Download The Future in Hair Transplantation

The Future in Hair Transplantation - NHI
1 of 28
The Future in Hair Transplantation
Journal of Aesthetic Dermatology & Cosmetic Dermatologic Surgery, Volume 1, Number 1, 1999, Pages 55-89
The Future in Hair Transplantation
Robert M. Bernstein, MD, William R. Rassman, MD, David Seager, MD
Walter P. Unger, MD, FRCP(C), Bobby L. Limmer, MD, Francisco Jimenez, MD
Jose M. Ruifernandez, Joseph F. Greco, PhD, PA/C, James Arnold, MD,
E. Antonio Mangubat, MD, Albert J. Nemeth, MD, Jung-Chul Kim, MD, PhD
Jennifer Martinick, MD, Edoardo Raposio, MD, FICS, Leonard M. Patt, PhD
Marty E. Sawaya, MD, PhD, Angela M. Christiano, PhD, Emanuel Marritt, MD
Abstract
The 1990's have witnessed major changes in hair transplantation, most notably the trend towards the use of large
numbers of very small grafts and the emergence of follicular unit transplantation as possibly the new "gold standard." This
article reviews the new developments that will shape hair restoration surgery as we enter the next millennium. Many
aspects of hair transplantation will be explored including: the follicular unit/mini-micrograft controversy, ways to measure
and maximize the donor supply, new concepts in graft storage, advances in wound healing, new instrumentation,
automated graft cutting and placing, advances in laser technology, the role of new medical treatments, and finally the
status of research in cloning and genetic engineering.
Introduction
Robert M. Bernstein, MD
The 1990's have witnessed major changes in hair transplantation, most notably the trend towards the use of large
numbers of very small grafts and the emergence of follicular unit transplantation as possibly the new "gold standard." In
addition to improved surgical techniques, new developments in medical treatments, marketing on the part of physicians,
and coverage by the media, have produced an increased public awareness of this rapidly evolving field.
The long-term observations of patients treated with the older hair transplant techniques and the use of new objective
means to measure donor supply, have made the modern hair restoration surgeon more keenly aware of the importance of
maximizing the patient's finite donor reserves. As a consequence, new ways of harvesting and dissecting donor tissue
have been developed to better preserve this supply, and new ways of handling and storing grafts awaiting placement
have been devised to enhance the viability of the grafts. In addition, long-term planning has assumed greater prominence
in surgical decisions. It is somewhat ironic that after four decades of wrestling with supply/demand issues, new
medications for hair loss may soon necessitate a complete re-thinking of the way we plan our procedures.
The use of large number of very small grafts has made the transplant process much more laborious and this has
prompted the development of new technologies to automate various aspects of the transplant process. Long transplant
sessions requiring greater numbers of staff and involving the movement of large numbers of small, fragile grafts has also
made quality control a central issue.
The decade has seen a dramatic decline in the popularity of scalp reductions and flaps, and fortunately the "pluggy look"
that was once the hallmark of many older transplant procedures is now deemed to be unacceptable. Unfortunately, many
patients still carry the telltale cosmetic deformities caused by the older techniques and "repair work" has become an
increasingly larger part of many physicians' practices.
The initial excitement over laser assisted hair transplants appears to have subsided, because the very tiny sites needed
in the newer procedures seems to be best made by cold steel incisions. However, laser technology is rapidly changing
and this tool may still have a future role in hair transplantation, possibly in ways we have not yet considered.
The development of 5-alpha reductase inhibitors and other medications that specifically attack the biochemical pathways
involved in androgenetic alopecia will have a profound influence on the future of hair restoration surgery. Once drugs are
able to successfully limit the extent of balding, supply/demand ratios will change, long-term planning may become less
important and the aesthetic demands of all patients may substantially increase. As medications become more effective,
their long-term safety profile established, and their use more widespread, it is possible that baldness may be preventable.
When this happens, surgery may be reserved for those already bald or for persons without significant androgenetic hair
loss who want to improve upon their natural attributes.
The Future in Hair Transplantation - NHI
2 of 28
Although hair loss in women is generally a far more significant cosmetic problem than in men, a much smaller proportion
of women are surgical candidates, since they generally exhibit a diffuse type of hair loss. When medications are
developed that are useful in women, an entire new population of patients may benefit from surgery. The increase in
female patients, might then more than offset any decrease in the number of procedures performed in men.
Cloning is another technology that has made significant progress in recent years and may supply the surgeon with an
unlimited source of donor hair. Genetic engineering, on the other hand, is a technology still in its infancy, but that may
someday render the hair transplant surgeon's role obsolete.
The move towards smaller grafts in the 90's has produced a number of controversies that are receiving a great deal of
attention in the hair transplant community. Among the most hotly debated are 1) the "supremacy" of the follicular unit over
traditional mini-micrografting, 2) the practicality of microscopic dissection, 3) the importance of single strip harvesting, and
4) the "ideal" transplant density. As this decade draws to a close, however, no issue is possibly more critical to the future
direction of surgical hair restoration as the debate over economy vs. quality.
The newer hair transplant techniques have enabled the surgeon to produce unprecedented naturalness, the ability to
complete the process in a smaller number of sessions, and the means to accomplish this with a more limited amount of
donor tissue. However, these newer procedures are technically more difficult, require a significant number of well-trained
staff, are more costly to deliver, and are too impractical for some cosmetic surgeons to perform. These limitations have
stimulated a number of enterprising physicians to try to facilitate the more tedious aspects of the procedure with the use
of automated devices.
Although much of the new technology has served to speed up the procedure, some mechanized devices accomplish this
at the expense of quality and the preservation of donor tissue. To what degree this occurs, and what its clinical
significance may be, still needs to be assessed in well-controlled, scientific studies. Until then, the subjective value that
surgeons and their patients place upon each of these aspects of the transplant may ultimately define the type of
procedures offered over the next few years.
As we approach the beginning of a new millennium, it is tempting to speculate about the future of hair restoration surgery.
This article has been a collaborative effort to review many of the new developments that will most likely shape this future.
The various opinions expressed in this article do not necessarily reflect the views of all the contributing authors and some
areas covered are so new that their practical value is not yet known. The purpose of this article is intended to be
provocative rather than dogmatic. We trust that the reader will enjoy our exploration into the future keeping this in mind.
Follicular Unit Transplantation – The End of the Evolution?
Robert M. Bernstein, MD
After four decades of evolution from the large plugs of the late 1950's to the extensive mini/micrografting of the early
1990's, possibly the central development in hair transplantation today is the recognition that the naturally occurring,
individual follicular unit may represent the ideal way in which to transplant hair. The underlying tenet of follicular unit
transplantation is that the follicular unit is sacred and should always be transplanted intact.1 While not all hair transplant
surgeons agree on the importance of using follicular units exclusively for the entire transplant, or in every patient, the
central role of this previously unrecognized anatomic structure in modern hair restoration surgery is without dispute.
Follicular units are distinct groupings of usually one to four, and occasionally five terminal hairs, surrounded by a
circumferential band of collagen called the "perifolliculum."2 It also includes one, or rarely two, vellus follicles, the
associated sebaceous glands, the insertions of the arrector pili muscles, and a neuro-vascular plexus. It has been
demonstrated that hairs seperated from other hairs of a follicular unit do not grow as well as the same number of hairs
transplanted keeping follicular units intact.3 The follicular unit is thus a physiologic, as well as an anatomic entity.
Follicular unit transplantation offers the surgeon the unique ability to transplant the maximum amount of hair with the
minimum amount of non-hair bearing skin. In this way, recipient wounds may be kept small, healing is facilitated, and with
proper technique, large numbers of grafts may be safely moved per session. The use of these discrete anatomic units
also helps to ensure that the cosmetic result of the transplant will appear completely natural.
In contrast to follicular units, micrografts (1-2 hairs), and mini-grafts (3-6 hairs), are small grafts cut randomly from donor
hair, not specifically as individual intact follicular units. They may consist of partial follicular units, single follicular units,
multiple follicular units, or multiple, partial follicular units.4 In mini-micrografting, the partial units may be at risk for
sub-optimal growth, and the multiple units will contain extra skin that will demand larger recipient sites. This, in turn,
causes more wounding to the recipient bed and may limit the number of grafts that can safely be transplanted in a
session.
It has often been said that with multiple sessions, minigrafts can look fairly natural in patients with ideal hair
characteristics. However, even in these circumstances, on close inspection, minigrafts can look unnatural compared to
follicular units. As the public becomes increasingly more discriminating, the future of hair transplantation is therefore likely
to involve an increasing demand for procedures that are performed using follicular unit transplantation exclusively.
The Future in Hair Transplantation - NHI
It is felt by most surgeons who perform follicular unit transplantation routinely, that single strip harvesting and complete
stereo-microscopic dissection are required to properly dissect follicular units from the surrounding tissue4. The reasons
for this are relatively straightforward. Harvesting with a multi-bladed knife will break up follicular units and transect
follicles, whereas removing the donor tissue as a single strip will yield the highest proportion of intact follicular units. Once
the single strip has been removed, the stereomicroscope, with its 10x magnification and intense illumination, will provide
the best visualization for the dissectors to accurately subdivide the strip and to isolate the individual units. Lower power
loop magnification does not provide sufficient resolution for precise follicular unit dissection and back-lighting will not
penetrate the intact strip.5
Although, it is hard to argue the supremacy of the follicular unit in theory, in practice, follicular unit transplantation is
tedious, demanding on the physician and staff, and requires a relatively high degree of expertise to be properly
performed. It is, therefore, reasonable to assume that in situations where follicular unit transplantation is impractical or
impossible, the patient might be better served by a more simple technique. In this vein, the standard practice of
mini-micro grafting is seen by some as a more practical alternative to follicular unit transplantation.
The advantages of mini-micrografting are that it is faster and requires less staff. In addition, it is felt that the damage
produced by the multi-bladed knife (used in mini-micrografting) is somewhat offset by the advantage of not having to
carefully trim around follicular units, which in itself can be a source of follicular injury (if not done with care). On the other
hand, in mini-micrografting, the slightly larger grafts and concomitantly larger wounds do not permit the total naturalness
that is achieved with follicular unit transplantation. In addition, the split follicular units and greater number of hair
fragments (produced by the use of the multi-bladed knife and less precise dissecting techniques) may result in less than
optimal growth.
The important factors affecting graft survival are still controversial. Graft trauma can take multiple forms. Do longer
transplantation procedures lead to greater graft desiccation, donor tissue anoxia (time-out-of-body) and lower yield or
does violating the follicular unit microanatomy lead to a lower yield? These important questions lack the controlled studies
required for meaningful answers, but the future direction of hair transplantation surgery may, in part, depend upon their
outcome!
As we will discuss in subsequent sections, new technology may soon substantially change how both follicular unit
transplantation and mini-micrografting are performed. However, regardless of how the technical parameters of each
procedure evolve, the debate of follicular unit transplantation vs. mini-micrografting will undoubtedly hold the attention of
the hair transplant community for years to come. In the meantime, the answer to which procedure is used may
unfortunately lie less with the needs of the individual patient, than with the resources and capabilities of the operating
surgeon and his staff.
REFERENCES
Bernstein RM, Rassman WR, Szaniawski W, Halperin A: Follicular Transplantation. International Journal of
Aesthetic and Restorative Surgery 1995; 3: 119-132.
Headington JT: Transverse microscopic anatomy of the human scalp. Arch Dermatol 1984;120: 449-456.
Seager D. Binocular stereoscopic dissecting microscopes: should we use them? Hair Transplant Forum Int 1996;
6(4): 2-5.
Bernstein RM, Rassman WR, Seager D, Shapiro R, et al. Standardizing the classification and description of
follicular unit transplantation and mini-micrografting techniques. Dermatol Surg 1998; 24: 957-963.
Bernstein RM, Rassman WR. Dissecting microscope versus magnifying loupes with transillumination in the
preparation of follicular unit grafts. A bilateral controlled study. Dermatol Surg 1998; 24: 875-880.
Larger Grafts – "Back to the Future?"
Walter P. Unger, MD, FRCP(C)
Is there a role for grafts larger than individual follicular units or small follicular families in hair transplantation? In at least
one of the "authors" view the answer is yes, and the reason is that it is felt that more density can be obtained by using
larger grafts. Limmer has reported using follicular grafting alone and achieving densities of 81 hairs per sq. cm1,2. I can
achieve over 200 hairs per sq. cm with standard grafts3. Since cosmetically excellent results are possible with 60-80 hairs
per sq. cm, and one can never be 100% sure of the ultimate donor/recipient ratio, more density is not a reasonable goal
for a majority of patients but this does not mean "all" of them.
The use of grafts that contain more than 2 or 3 follicular units (or families), is generally limited to 10 to 15% of the patient
population who a) want greater density, b) can afford greater density in terms of long term donor/recipient area ratio
(usually because of an appropriate combination of family history, patient age and a positive physical examination), c)
ideally have some persisting hair in the recipient area so any potential for transitory plugginess is minimized, and d)
ideally have advantageous hair characteristics such as fine texture and light color, to minimize any possibility of
transitional plugginess. Given the above parameters, very little transitional plugginess, if any, is noted by patients or
people who see them and therefore the "price" of transitional plugginess is eliminated from the "price" the patients have to
pay for this greater density. A zone of micrografting and minigrafting is always used anterior to the larger grafts to create a
more natural looking hairline zone and to help camouflage the larger grafts. In addition larger grafts are never used in the
3 of 28
The Future in Hair Transplantation - NHI
posterior half of a patient with Type V or greater male pattern baldness (MPB).
Individuals who choose to use larger grafts must also be aware that, theoretically at least, the area treated with larger
grafts must eventually be filled solidly (when all original hair has been lost). If not, when the hair is parted through the
transplanted area, when it is wet or wind blown, plugginess may be noted. However, the density is usually so great that
this is generally unnecessary even for relatively demanding patients.
The other type of patient in whom standard grafts are advantageous, are individuals who have been treated with standard
grafts in the past and have obvious spaces between them with a so-called "Barbie-doll" appearance. If there is good hair
density in the standard grafts on either side of a hairless space, the most efficient way of eliminating that space is to fill it
with an appropriate sized graft containing hair of similar density to the flanking standard grafts. Punching out a portion of
some of the larger grafts can be most useful as an adjunctive technique for this problem, rather than an alternative one.
Although it has been claimed that good hair yield cannot be accomplished if standard grafts are used5, Nordstrom
showed a 90% survival6 and Unger showed a 90-110% survival7 in studies carried out many years ago. In addition,
although it has been said that solid filling with standard size grafts is impossible, this has not been the experience of
everyone. The argument that you need great expertise and practice to accomplish similar results and therefore most
people cannot create this, is a self-fulfilling prophecy. One should aim for this level of expertise rather than abandon any
attempt of achieving it.
Even physicians, who are generally follicular unit transplant enthusiasts, are again trying the use of larger grafts,
containing more than one follicular unit, to produce more density. With time they may develop the confidence to try still
larger grafts in properly selected patients. It is the hope of at least one of these authors that this trend will continue, so
that the value of larger grafts once more becomes more generally recognized.
REFERENCES
Limmer B: The Density Issue in Hair Transplantation. Dermatol Surg 1997; 23: 747-750.
Limmer B: The Density Issue, A debate that refuses to die. Hair Transplant Forum Intl. 1998; 8(3): 1,4-6.
Unger W: Different Grafts for Different Purposes. Amer Jour Cos Surg 1997; 14(2):177-183.
Unger W: Graft types. Hair Transplant Forum Intl. 1998; 8(3): 14-16.
Seager D: Comments. Hair Transplant Forum Intl. 1998; 8(3): 16-17.
Nordstrom REA: Evaluating the Efficacy of the punch hair grafting technique. J Dermatol Surg Oncol 1989; 15:
404-408.
Unger W: Hair Counts: A Scientific approach to the evaluation of various factors in the survival of hair transplants.
Hair Transplantation, 1st Edition, Unger W(Ed), Marcel Dekker Inc., 1979, Appendix E, P. 203-210.
Maximizing the Donor Supply
Bobby L. Limmer, MD
Since all hair restoration procedures involve the redistribution of preexistent hair, the donor supply remains an important
limiting factor in hair restoration surgery. For this reason, it is absolutely essential to preserve the maximum number of
viable hair follicles in every procedure. Any avoidable cause of follicular wastage should be unacceptable to both the
physician and the patient. Combining the follicular sparing aspects of single-bladed donor harvest, microscopically
magnified dissection of follicular unit grafts, and careful, gentle implantation methods, consistently produces a growth rate
of 90-95% of the harvested hair1. Although only a relatively small percentage of hair transplant surgeons currently utilize
optimal harvesting techniques, this number should increase as the importance of preserving the donor supply is more
widely recognized.
THE DONOR AREA
The punch autograph technique of Orentreich2, the multi-bladed knife excision method of Vallis3, and the single bladed
donor harvest of Uebel4 have individual advantages and disadvantages. Simple mathematical analysis of the length of
the surgical excision required to harvest 10 cm square area of donor tissue clearly reveals that the punch technique
requires 5 times as much surgical margin as a single ellipse, and the multi-bladed knife (utilizing four blades with 3 mm
spacing) requires 2.5 times as much excisional margin as a single bladed knife5. When the mathematical advantages of
such significantly less surgical margins are combined with the advantage of direct intra-operative visualization of the
single bladed knife excision throughout the excision process, the use of single-bladed knife for the donor harvest
obviously becomes the most follicular sparing method.
It has been the experience of some of these authors that when comparing the percentage of hair follicles that are
transected by multi-bladed vs. single bladed knife harvest reveals a significant difference in follicular transection rate. The
single bladed knife will transect approximately 2-3% of all follicles in total donor tissue harvested compared with 12-16%
follicular transection rates for multi-bladed knives utilizing 4 blades spaced at 3 mm widths between blades. When the
blade spacing is decreased, the amount of transection increases dramatically.
GRAFT DISSECTION
4 of 28
The Future in Hair Transplantation - NHI
Historically, grafts for transplantation have typically been "cut to fit" specific recipient site and sizes. Such "cut to fit"
methods ignore the natural growth pattern of follicular units as they occur within the donor's scalp. Microscopic dissection
and implantation of naturally occurring follicular units as the basic graft methodology used since 1988 by Limmer6 has the
advantage of not only preserving the maximum number of undamaged hair follicles for transplantation but also has the
advantage of generating small, clean grafts which allow for much denser packing. In the hands of an experienced
assistant, the transection rate during graft production is characteristically less than 3% of all follicles in the donor tissue.
Cooley and others7 found the transection rate to be approximately twice as high when utilizing back lighting and loupe
magnification techniques compared with the dissecting microscope. Additionally, Bernstein and Rassman8 have shown
that even partial microscopic dissection of the donor tissue produces a 17% greater yield of hair for transplantation when
compared with loupe dissection with transillumination. If total microscopic dissection were compared, certainly the
percentages of hair available for transplantation would be significantly increased above this 17% figure, probably on the
order of an additional 5-10%. Most importantly, the high resolution and intense illumination of the microscope allows for
the dissection of an intact donor strip and obviates the need to "pre-cut" the strip with a multi-bladed knife in order to
make the subsequent dissection easier and thus eliminate this source of follicular injury as well.
REFERENCES
Limmer BL: Survival of Micrografts. In: Hair Replacement. Stough DB, Haber R. St Louis Mosby Press 1996;
147-149.
Orentreich N: Autografts in Alopecias and Other Selected Dermatological Conditions. Ann. N.Y. Acad. Sci. 1959;
83: 463.
Vallis CP: Surgical Treatment of the Receding Hairline. Plast Reconstr Surg 1968; 33: 247.
Uebel CO: Micrografts and Minigrafts: A New Approach for Baldness Surgery. Ann Plast Surg 1991; 27: 476-487.
Limmer BL: The Donor. In: Hair Replacement. Stough DB, Haber R. St Louis: Mosby Press 1996; 142-143.
Limmer BL: Elliptical Donor Stereoscopically Assisted Micrografting as an Approach to Further Refinement in Hair
Transplantation. Dermatol Surg Oncol 1994; 20: 789-793.
Cooley JE: Follicle Trauma in Hair Transplantation: Prevalence and Prevention. Presented at Int Soc Of Hair
Restor Surg, 5th Annual Meeting, Barcelona, Spain. Oct 15-19, 1997.
Bernstein RM, Rassman WR: Dissecting Microscope vs Magnifying Loupes with Transillumination in the
Preparation of Follicular Unit Grafts. A Bilateral Controlled Study. Dermatol Surg Dermatologic Surgery 1998; 24:
875-880.
New Ways to Quantify Hair Movement
Francisco Jimenez, MD and Jose M. Ruifernandez
Since hair transplantation is essentially a redistribution of a limited amount of hairs from one circumscribed area of the
scalp (donor area) to another (recipient zone), the whole process of hair movement can be mathematically modeled. The
advantages of this mathematical analysis are:
To develop an objective method of surgical planning that is reproducible.
To evaluate the efficiency of a hair transplant by comparing the final result with the proposed theoretical
estimations.
To save as much donor hair as possible due to its finite supply.
DISTRIBUTION OF HAIR IN THE DONOR AREA
Human hair emerges from the scalp in groupings containing one to four and rarely five hairs. In the average Caucasian
individual, most of the hair follicles emerges from the scalp as two hair follicular units (approximately 55% are two hair
follicular units, 35% are three, four and five hair follicular units, and 10% are one hair follicular units). However, there is a
clear correlation between the hair density (number of hairs per square centimeter) and the relative proportion of one to
four hair follicular units. For instance, individuals with average and high hair density have more numbers of three hair
follicular units than one hair follicular units, but individuals with low hair density (less than 130 hairs/cm2) have more one
hair units than three hair units.
These correlations can be expressed with the following mathematical equations, which are explained in greater detail
elsewhere1:
n = 0.29 x d + 27
n1= -0.16 x d + 36
n2= 0.19 x d + 9
n3= 0.26 x d – 18
Where,
d = hair density (number of hairs /cm2)
n = follicular unit density (total number of follicular units / cm2)
n1= number of one hair follicular units / cm2
5 of 28
The Future in Hair Transplantation - NHI
6 of 28
n2= number of two hair follicular units / cm2
n3 = number of three, four, and five hair follicular units /cm2
Note: Due to the scarcity of four and five hair follicular units and for the sake of simplification, all four and five hair
follicular units are considered as three hair units.
After measuring the hair density with a densitometer, or an equivalent quantifying instrument, the hair transplant surgeon
can use these equations to calculate the follicular unit density and the expected proportions of the hair groupings. The
results obtained by the former equations are "most probable median values" for a specific hair density. As occurs with any
statistical mathematical model applied to a biological system, a small percentage of error can be expected. Significant
variations in the hair distribution (hair density and follicular density) have been noted among different races2, which make
the above equations useful only for Caucasians.
The distribution of the hair in one- to four-hair follicular units is what mainly determines the great genetic variability in hair
density, rather than the actual spacing of follicular units, which is relatively constant. There is also a dynamic change in
the proportion of follicular units due to the progressive hair loss pattern associated with androgenetic alopecia.
The early stages of androgenetic alopecia are marked by the progressive diminution of hair shaft diameter and a
decrease in length, caused by a shortening of the hair growth cycle. These changes seem precede actual hair loss. It
appears that as male pattern baldness progresses, the hair is lost as single hairs from all types of follicular units, in the
same proportion. Therefore, the three hair units will be converted into two hair units, the two hair units into one-hair units,
and some of the one-hair units gradually disappear, although new one-hair units will be formed from preexisting two hair
units. As a result (although the hair density varies significantly), the total number of follicular units per square centimeter
remains between certain limits until the individual reaches a significant degree of alopecia3.
EVALUATION OF THE RECIPIENT SITE
To measure the recipient area is very important for planning a hair transplant session. Depending on the area in square
centimeters to be transplanted, the surgeon can predict the number of recipient sites to be made and, subsequently, the
number of follicular units needed from the donor area.
A simple method to measure the recipient area is to use a flexible and transparent calibrated reticula that accommodates
to the curved shape of the scalp. A more accurate instrument, however, could be an electronic planimeter, which by
outlining the borders of the recipient zone can give us the exact measurement of the area. As far as we know, this
instrument has not yet been adapted for use in hair transplantation.
The density of a hair transplant (number of hairs transplanted per square centimeter) is always an object of debate in
meetings and scientific journals. We believe it is a mistake to link density exclusively with graft size (the argument is made
in favor of larger grafts producing more density than smaller grafts), and that a much more critical factor is the number of
recipient sites made per unit area (or how close the follicular units are placed)4. A recent in vivo study by Limmer5
compared the density achieved using the mini-micrografting technique with that accomplished by standard grafts,
showing that comparable or even better density could be obtained with the mini-micrografting approach (average density
of 64 hairs/cm2 after four plug sessions versus an average density of 61 hairs/cm2 along the first centimeter of frontal
hairline after only 1 session of mini-micrografting).
To achieve densities in the order of 60 hairs/cm2 with randomly placed follicular units, it is necessary to create from 25 to
40 recipients sites per square centimeter depending upon the donor density of the patient and the size of follicular units
used in a specific area. In adition, when using follicular units, the surgeon can dictate the density not only by changing the
number of recipient sites made per square centimeter, but also by planning the distribution of the follicular units. For
example, larger follicular units might be placed in those areas where maximum density is desired, such as in the central
forelock. If the larger 3- and 4-hair follicular units are sorted and used in select areas, it is relatively easy for an
experienced surgical team to achieve these densities with only 20 sites/cm2.2
When discussing hair transplant density, an effort should be made to always present numerical data (number of recipient
sites made per square centimeter and the average number of hairs placed in each site), while avoiding nonspecific terms
such us "dense packing," which only adds confusion.
"APPARENT DENSITY" AND COMPUTER IMAGING
Besides the "real density" (number of transplanted hairs per square centimeter as discussed above), there is another
factor that plays an important role in the final cosmetic result and in the illusion of density, which is what we call the
"apparent density." The apparent density depends upon a number of factors including the actual number of hairs per cm2,
hair shaft diameter, wave, color, skin/hair color contrast, the emergent angle of the hair, and a number of less tangible
factors such as intrinsic oiliness or integrity of the hair shaft cuticle. Some of these factors may play an even greater roll in
the apparent density than the absolute number of hairs per se.6
An instrument that is able to measure the "apparent" density still needs to be developed. It is obvious that a computer
system that just takes into account the total number of hairs transplanted could not possibly predict aesthetic results of
The Future in Hair Transplantation - NHI
7 of 28
the surgery. In theory, if the total number of hairs transplanted, the resultant density per unit area, hair shaft diameter, hair
color, wave, skin color, and styling, could all be accounted for, then computer imaging might accurately represent what a
transplant might achieve in a particular individual.
Computers are certainly going to play a more significant role in the future of hair transplantation by assisting the surgeon
in the overall surgical planning and in the quantification of the hair moved in a transplant. They can be used as measuring
tools as well as imaging systems. Using a video digital computer system, the patient's recepient zone can be captured on
the screen. Then, the computer would measure the area, and the surgeon could draw different areas in the recipient
zone, assigning a real density to each one of them. In addition, the donor site could be scanned by the computer,
obtaining the hair density, the follicular density, and other salient features that would affect the outcome of the surgery.
After integrating all these data, the computer could give the surgeon a number of recommendations such as:
The size of donor strip to be excised.
The number of incisions to be made in the recepient zone or in the different areas in which the receptor zone was
subdivided, according to the real hair density proposed.
The estimation of the final apparent density based on the real densities assigned to the recepient zone or to
different areas of the recepient zone.
A virtual image representation of the final outcome according to the proposed alternatives.
Hopefully, the time for computers to reach this level of sophistication is close at hand.
REFERENCES:
Jimenez F, Ruifernandez JM: Superficial distribution of human hair in follicular units: a mathematical model for
estimating the donor size in follicular transplantation. (Submitted for publication to Dermatol Surg)
Bernstein R, Rassman WR: The aesthetics of follicular transplantation. Dermatol Surg 1997; 23: 785-99.
Bernstein RM, Rassman WR, Szaniawski W, Halperin A: Follicular transplantation. International Journal of
Aesthetic and Restorative Surgery 1995; 3: 119-132.
Stough D, Jimenez F, Potter T: A redefinition of male pattern baldness. Dermato Surg 1996; 22: 484-5.
Limmer BL: The density issue in hair transplantation. Dermatol Surg 1997; 23: 747-50.
Bernstein RM: Measurements in Hair Restoration. Hair Transplant Forum Intl. 1998; 8(1): 27.
Controlling The Human Factor in Graft Injury
Joseph F. Greco, PhD, PA/C
In 1984, Drs. Shiell and Norwood first described the existence of X-factor1 as something producing unexpected and
unexplained poor results in 4-mm grafts that occurred in less than 1% of the cases.
It was conjectured that some sort of antibody reaction rejection process produced localized graft ischemia.2
The emergence of the megasession in the early 1990's brought new reports and concerns of no growth and poor growth
in large micrografting sessions. In 1994, Greco postulated the existence of H-factor as the primary cause of decreased
micrograft survival. H-factor would be any "subtle or invisible iatrogenic trauma to the follicular growth center" that
occurred during the operative process, resulting in decreased growth or no growth.3 The H-factor can occur during or
between any phase of the transplant procedure. The effects may be categorized as either primary or secondary H-factor.
In primary H-factor, the insult is directly caused by the surgeon or the assistant. Dr. Seager nicely demonstrate this with
his "skinny" and "chubby" micrograft study,4, which demonstrated decreased growth in the over aggressively dissected
follicular units. Dr. Seager conjectures that poor growth also results from the "disruption of the physiological and
anatomical bond between the hairs of naturally existing follicular clumps."5
Another example of primary H-factor demonstrates that "crush injury"6 to follicular growth centers during the placement of
grafts caused a decreased rate of growth in roughly handled micrografts. Drs. Cooley and Vogel clearly demonstrated the
effects of delayed or no growth when the dermal papilla was traumatized at a weak point just above the papilla during
harvesting, dissecting and placement.7
Secondary H-factor occurs as a result of predisposing follicular units to damage. Dr. Gandelman demonstrated a
decreased growth in micrografts when follicular units were exposed to the damaging effects of drying and increased
temperature.8 Additionally, if a surgeon does not provide adequate hemostasis when densely placing follicular units,
bleeding may cause secondary H-factor, because the units may be over-handled by assistants during the placement
phase.
Additional studies on micrograft survival by Dr. Limmer,9 tissue hypoxia studies by Dr. Goldman,10 and reduced
oxygenation studies by Drs. Kemp and Kansted,11 address various causes for decreased micrograft yield in
megasessions. Because of these and other studies that pinpoint the etiology of H-factor, technical advances have led to a
"quantum leap" in micrograft survival in total micrografting sessions. Advancements have come in each phase of the hair
transplant procedure, as well as tissue care throughout the transplant procedure.
The trend away from small strips toward the elliptical excision has dramatically decreased overt follicular transection.
The Future in Hair Transplantation - NHI
8 of 28
Interestingly, this is a return to the original megasession procedure, or "punctiform method", developed by Dr. Carlos
Uebel in 1986.12 There have been many attempts to automate the micrograft dissection process with varying degrees of
success. However, most automated sectioning developments subjected harvested tissue to H-factor.
The development of back-light technology with loop magnification for transilluminated microdissection, as first reported by
Dr. Paul Rose,13 allowed better visibility of light colored follicular units when compared to traditional methods of
sectioning. However, the greatest advance in reducing H-factor during micro-dissection was the introduction of the stereo
microscope by Dr. Limmer. 14 Recent studies by Dr. Bernstein and Rassman,15 indicate an increase in follicular unit
grafts, as well as 17% increase in the total amount of hair harvested from the donor strip when using the dissection
microscope as compared to magnifying loops with transillumination. Their studies show this while examining only the later
phases of dissection. The differences are more significant when the microscope is used for the entire dissection process.
The introduction of chilled Petri dishes to keep the dissected grafts below room temperature has led to increased graft
survival. Handling grafts in the proper anatomical zones, avoiding the lower to mid-portion of the follicle containing the
dermal papilla and epithelial cells,16 avoiding over-handling and rough handling between each phase, and meticulous
attention to detail by the entire team, has led to decreased incidents of H-factor.
The movement towards 16- and 18-gauge needles, as well as small lancets from the punches, has had a direct
relationship in decreasing recipient site trauma and increased follicular yield in the densely placed follicular unit
transplantation sessions. There are currently first generation automated placement instruments,17 so time and critical
review will determine the effectiveness of automating the placement phase and reducing H-factor.
In sum, H-factor in total micrografting sessions has decreased with:
the development of finer placement instrumentation
improved placement techniques
overall attention to the negative effects of rough handling
attention to the negative effects of exposure to air and temperature
the use of microscopes for dissection and magnification for placement
an overall awareness and attention to detail during each phase of the transplant procedure.
In the final analysis, the advancements in effectively reducing H-factor since the early 1990's have been effective because
of the numerous, previously mentioned studies and the collective thinking and action of numerous hair surgeons.
Advanced technology, such as computer generated scanners for dissecting follicular units, may make it possible to
automate the dissecting process, while preserving the integrity of the follicular unit, thus reducing H-factor even further.
Second and third generation automated graft placement instruments will speed up the graft placement phase, as well as
reduce follicular trauma. Regardless of technology, the most important and effective measure in controlling H-factor now
and in the future is attention to detail throughout every phase of the hair transplant procedure.
REFERENCES
Norwood, O.T., Schiell, R.C.: Hair Transplant Surgery, 2nd edition. Springfield, IL: Charles C. Thomas, 1984.
Schiell, R.C.: Whither the X-factor. Hair Transplant Forum Intl. 1996; 6(4): 13.
Greco, J.: Is It X-Factor or H-Factor? Hair Transplant Forum Intl. 1994; 4(3): 10-11.
Seager, D.J.: Micrograft Size and Subsequent Survival. Dermatologic Surgery 1997; 23: 757-761.
Seager, D: Binocular Stereoscopic Dissection Microscopes: Should We Use Them?, Hair Transplant Forum Intl.
1996; 6(4): 2-5.
Greco, J., Kramer, R.: Presentation on Follow-up "Crush Study". Intl. Soc. of Hair Restoration in Barcelona, Spain,
October 15-19, 1997.
Cooley, J., Vogel, J.: Loss of the Dermal Papilla During Graft Placement: Another Cause of X-factor? Hair
Transplant Forum 1997; 7(1): 20.
Gandelman, M.: Presentation on Micrograft Survival, ISHRS 5th Conf., Barcelona, Spain, October 15-19, 1997.
Limmer, B.L.: Micrograft Survival. IN: Stough, D.B., Haber, R.S., eds. Hair Replacement, Medical and Surgical: St.
Louis, Mosby: 1996: (5) 147-9.
Goldman, B., The Effects of Hair Micrograft Surgery on Scalp Oxygen Levels. Presentation at 3rd ISHRS Meeting,
Las Vegas, Nevada, 1995.
Klemp, P., Kansted, B.: Subcutaneous Blood Flow in Early Male Pattern Baldness. J. Dermotol 1989-92; 725.
Uebel, C.O.: Punctiform Technique with Micrografts - A New Method for Pattern Baldness Surgery. Free Paper
Presented at Jornada Carioca Cirur Plast., Rio de Janeiro, Brazil, August, 1986.
Rose, P.: Presentation American Society of Hair Restoration Surgery in Orlando, FL, 1996.
Limmer BL: Elliptical donor stereoscopically assisted micrografting as an approach to further refinement in hair
transplantation. Dermatol Surg 1994; 20: 789-793.
Bernstein RM, Rassman WR.: Dissecting microscope versus magnifying loupes with transillumination in the
preparation of follicular unit grafts. A bilateral controlled study. Dermatologic Surgery 1998; 24: 875-880.
Cooley, J., Vogel, J.: Loss of the Dermal Papilla During Graft Placement: Another Cause of X-factor? Hair
Transplant Forum 1997; 7(1): 20.
Rassman WR, Bernstein RM.: Rapid Fire Hair Implanter Carousel: A new surgical instrument for the automation of
The Future in Hair Transplantation - NHI
9 of 28
hair transplantation. Dermatol Surg 1998; 24: 623-627.
The Future in Instrumentation
James Arnold, MD
The imaginative minds of many surgeons have given us a glimpse of future developments in hair transplantation
techniques and instrumentation. Efforts to simplify the work or to combine tedious steps include devices to automatically
insert grafts, to cut donor tissue into multiple grafts in a single pass, and to lessen crush damage to grafts are surfacing.
The recipient site has recently received a new focus of interest among transplant surgeons reflecting a desire to lessen
the traumatic effects, which occur from cutting hundreds of recipient sites in close proximity. New instrumentation has
been developed with the intended goals of preserving the blood supply and minimizing scarring to the scalp. The concept
of cutting recipient sites to an absolute minimum depth is based on the anatomical design of the vasculature supplying
blood to the scalp1.
Montagna2 and others have demonstrated the primary distribution of blood to all areas of the scalp is through a network
of arteries that lie beneath the dermis. This arterial system is strictly confined to the fatty, sub-dermal compartment with
even the smallest arteriole rarely entering the dermal portion of the scalp. Small ascending vessels bring blood to the
dermis, which is then distributed, through a vast network of capillaries, supplying the appendages of the dermis including
the follicles. For the transplant surgeon, it is important to recognize that the basic arterial system lies totally beneath the
dermis, while the dermis proper is supplied with capillaries alone. The importance of this information is related to the
ability of the scalp to readily heal damaged capillaries. In contrast, the healing mechanisms for the underlying arterial
network are more limited.
Capillaries have an outer wall of only a single cell in thickness and are replaced quickly if severed or damaged, via the
process known as angiogenesis. Vessels of the arterial system, even the smallest arteriole, are compound structures with
an endothelium lining, a muscular wall and an outer sheath. Re-canalization of arteries may occur, and existing
anastomosis may expand, but neither response will be as efficient for providing blood to the scalp as the original arterial
system. The concept of minimal depth recipient sites, therefore, is to limit cutting of the sites to the capillary dermis and
avoid penetrating into the sub-dermal region where permanent compromise to blood supply may occur. In general, the
capillary dermis is thick enough to allow recipient sites 3-4mm in depth without penetration into the sub-dermal
compartment. Recipient sites 3-4mm deep are generally adequate in depth for transplant grafts.
There are several challenges for the surgeon in cutting minimal depth recipient sites. First, the depth of each site should
extend the full 3-4mm, no less and no more. Second, the sites should be fully open at the base of the site to adequately
accommodate the base of the graft.
In the past, lancet or spear-point shaped blades were popular among transplant surgeons for cutting recipient sites.
Lancet blades, such as hypodermic needles, No-Kor needles, #11 scalpel blades, and spear point blades have a sharp
point which facilitates penetration of the scalp. However, to open the deeper portion of the recipient site, lancet and
spear-point blades must extend beyond the 3-4mm minimum, usually penetrating well into the territory of arterioles. A
better design is a chisel-shaped blade, as the blade will cut an opening of uniform width along the entire length of the
incision. In order for the flat, chisel-shaped blade to penetrate the scalp as easily as a pointed blade, the chisel must be
extremely sharp. To control depth, limiting penetration 3 to 4mm, a "stop" can be used.
An instrument designed specifically for cutting minimal depth recipient site is the Min-de Knife TM (A to Z Surgical, Inc.
San Jose, California). The instrument has a chisel blade sufficiently sharp to penetrate the scalp easily and the blade
handle acts as a stop to control cutting depth to either 3mm, 3.25mm, 3.5mm or 4mm. Surgeons familiar with the
instrument describe less bleeding occurring in the recipient area. As evidence of this, minimal depth incisions ooze from
the dermal capillaries, but active bleeding from punctured arteries occurs less frequently than with lancet or spear-shape
blades.
There is no doubt that many improvements will continue to evolve in the field of hair transplantation. While the basic
techniques will remain the same, new methods and instruments will greatly simplify the process.
REFERENCES
Arnold, J.: What's new in techniques and instrumentation? American Academy of Dermatology Annual Meeting,
February 27-March 4, 1998, Orlando, Florida. (AAD Audiotape 320A and B)
Montagna, W. Parakkal PF: The Structures and Function of the Skin. New York cademy Press 1956
Automated Graft Cutting
E. Antonio Mangubat, MD
The future of hair restoration surgery (HRS) lies in technology and automation. Contemporary HRS differs from most
other cosmetic procedures in its high demand of skilled manpower, great dependence on non-physician assistants and
prolonged procedure times. Our noted colleagues, including Marritt, Limmer, Seager, Bernstein, Rassman and others,
have taught us the value of large numbers of small grafts in producing natural results. Rassman and Bernstein go on to
The Future in Hair Transplantation - NHI
advocate the exclusive use of follicular units in HRS.1
Although the HRS community universally recognizes the value of small grafts, there is still much controversy as to which
methods yield the best results. Furthermore, managed care pressures have caused the influx of new HR surgeons
creating intense market competition never before seen in HRS history. These forces have influenced the HRS community
to become faster, more efficient yet strive for the best results.
The nature of contemporary HRS is repetitive tasks: 1) graft cutting and 2) graft placement. With the exception of a few
individual patient variations, these tasks are virtually identical for all patients undergoing HRS. Repetitive tasks naturally
lend themselves to automation. The focus of this section is the automation of graft cutting. The ideal graft cutter would
produce large numbers of hair grafts with uniform size and shape and without follicular damage. The grafts would all be
viable, easier to place and procedure times would be significantly reduced.
The use of impulsive force to significantly improve the quality of grafts processed with an automated graft cutter has been
recently introduced into hair transplantation.2 Impulsive force is a physical concept defined by the equation:
Where ðDt is the duration of time during which the external force is applied.3 A cursory examination of the equation
demonstrates that the smaller ðDt for any given external momentum, the larger the impulsive force. Many common uses
of impulsive forces are seen today including splitting wood with an ax, hitting a golf ball and a martial arts expert breaking
bricks with a bare hand. The feasibility of these examples could not be explained without this physical concept. The latter
example is most striking with a human hand applying a small external force for a very brief period of time producing
impulsive forces large enough to break the brick material which is many times harder than human flesh. Prior graft
preparation devices do not take advantage of this physical property and thus crush injury to the grafts may occur,
especially if the blades have been dulled by prior use.
The impulse graft cutter consists of a stable base and three sets of parallel spacer bars, which hold the cutting blades
rigidly in place. A series of long 1.0 mm donor strips are then taken with a multi-bladed knife. Harvesting high quality
donor strips with a multibladed knife is greatly technique-dependent4 and is critical to successful graft cutting automation.
After trimming the excess fat and separating the donor strips, a strip is placed on the graft cutter carefully aligning the
follicles with the cutting blades. A wooden tongue blade is used as a force spreader to cover the donor strip and hold it
firmly in place while a rhinoplasty mallet is used to impart the impulsive force to the donor strip. Impulsive force then
causes a clean shearing of the tissue with surprising little transection.
Follicular trauma can take many forms including transection, desiccation5,6 and prolonged tissue anoxia (timeout-body)7. Although graft cutting automation may potentially increase the risk of transection, it reduces the risks of
desiccation and donor anoxia by the significant reduction in procedure times. In addition, automation decreases
expenses, dependency on skilled staff, training requirements and ameliorates the disruption of staff turnover. The graft
cutter places the responsibility of quality graft production back in the hands of the surgeon.
A major challenge that lies ahead is to make HRS more affordable. The expense of HRS lies in its time consuming
nature. Technology will ultimately make HRS more affordable through efficiency, speed and reproducible results. This era
in HRS is upon us.
REFERENCES
Bernstein RM, Rassman WR, Szaniawski W, Halperin A: Follicular Transplantation. International Journal Of
Aesthetic And Restorative Surgery 1995 3:119-132.
Mangubat EA. Impulsive Force: A New Method To Cut Grafts. International Journal of Cosmetic and Restorative
Surgery 1998. 6:19-23.
Halliday D, Resnick R. "Collisions" In Fundamentals Of Physics, P 155-161, John Wiley & Sons, Inc., 1970
Arnold J: Pursuing The Perfect Strip: Harvesting Donor Strips With Minimal Hair Transection. International Journal
of Aesthetic and Restorative Surgery 1995. 3:148-153.
Gandelman M: Light and Electron Microscopic Analysis of Injured Grafted Micrografts. Presented at the
International Society of Hair Restoration Surgery, November 1997, Barcelona, Spain.
Gandelman M: Light And Electron Microscopic Analysis Of Injured Grafted Micrografts: Stage II. Presented at the
International Society of Hair Restoration Surgery, September 1998, Washington, DC.
Limmer BL: Micrograft Survival In Hair Replacement: Surgical And Medical. Pg. 147-149. DB Stough And RS
Haber Eds. Mosby. 1996
COMMENTARY
The purpose of this section has been to introduce a new device that may significantly reduce the time and labor involved
in graft dissection. In spite of its potential benefits, some of the co-authors have concerns about the automated graft
10 of 28
The Future in Hair Transplantation - NHI
11 of 28
cutting technique for the following reasons:
It is important to stress that the growth rate and clinical significance of transected hair follicles, either produced by the
multi-bladed knife during harvesting, or from other aspects of the dissection process, has not been examined in well
controlled studies and is, at the present time, highly controversial. The successful use of the impulsive technique depends
upon the generation of very thin strips using the multi-bladed knife. The experience of some of these authors has been
that even with 3mm spacing, the multi-bladed knife can cause significant and unacceptable damage to the donor tissue.
The very thin, 1 to 2 mm strips needed for this technique would be expected to cause even greater transection.
Dr. Kim reported an increased incidence of pseudocyst formation when transected follicles are implanted, especially the
lower portion. At this time the clinical impact of this finding is unclear. Avoiding follicular injury, especially transection, is in
part dependent upon the ability of the relatively rigid follicular structures to be pushed aside during follicular dissection, as
the cutting instrument passes through the surrounding dermis and subcutaneous fat. In theory, the rapid impact of the
impulsive technique should decrease crush injury to grafts; however, it is also possible that by essentially "freezing" the
tissue in place during the rapid impulsive force, follicular transection may actually increase. Well-controlled studies are
needed in each of these areas.
Robert M. Bernstein, MD
Automating Graft Placement
With many physicians now converging on a single standard of quality (the follicular unit),1 the focus of hair transplantation
is now moving to solve the problems addressing the cost of the procedure in terms of labor, time and money, and in the
consistency and predictability of product. Newer techniques have evolved which move more hair in smaller and smaller
units. More labor has been neeeded to deal with the increasing workload that these new techniques require. Labor
intensive processes produce human variables, which lie at the heart of the problems defined herein. As the laborintensive process is solved, costs will fall and quality of product will rise. The new standard of quality will then be in the
reach of all physicians performing cosmetic hair restoration surgery.
Most surgical procedures utilize only one or two assistants as the surgeon performs the procedure. In hair restoration, the
surgical procedure is largely performed by a large technical staff because it has become tedious, time consuming and
monotonous. At times, the procedure becomes unmanageable and, in response to this, the surgeons have abdicated
quality control to the technical staff doing the work. Results vary with the expertise of the staff and consistency becomes a
hit-or-miss process. If a surgeon is fortunate to have good surgical management skills and a dedicated, loyal and stable
staff, results will be more predictable. However, this should not be a precondition for quality surgery.
Automation lies at the heart of the solution for it can address problems of speed and quality, as well as allowing the
surgeon to more easily regain control over the surgical process. The automation solution should accomplish the following
goals:
1.
2.
3.
4.
5.
6.
7.
Reduce surgical time to under 3 hours for a typical surgery.
Reduce labor to a surgeon and one or two assistants.
Reduce or eliminate many of the human variables associated with the surgical procedure.
Reduce the stress of the procedure on the surgeon and staff.
Reduce the training and skill requirements for the surgical staff.
Reduce graft damage from manipulation and/or drying.
Reduce the need for human quality control processes other than with the surgeons direct involvement.
Make the procedure safer for the patient so that it produces less trauma by reducing (a) medication, (b) anesthesia time,
(c) wounding, (d) bleeding and (e) tissue exposure to hostile environmental factors. To accomplish this, the various
process involved in the hair transplantation process must be rethought and reengineered. For simplicity, the process can
be divided into two phases: graft harvesting, and graft placement. Automation should be able to simplify the entire
process either step-by-step or through some generally integrated solution. The current discussion addresses new
instrumentation designed to facilitate the second phase of this process, namely graft placment.
Traditionally, sites (wounds) were created in the recipient area and grafts were placed into the pre-formed sites in a
second step. In the traditional manual process, the grafts were handled a number of times, often exposed to drying at
points along the way. During the placement phase, as in the dissection phase, graft damage and desiccation had to be
minimized. Grafts were often grasped and squeezed repeatedly in the growth regions of the follicles, as staff members
tried to implant them into the scalp.
Graft placement is a very delicate process and learning how to manually place the grafts in a competent and efficient
manner, with minimal trauma, often requires months or years of experience. Preventing graft drying is equally important
and ignoring these two important factors will negatively impact graft growth.
Automation devices available today include the Choi Hair Transplanter2 and the Rapid Fire Hair Implanter Carouseltm3.
A third, the Hair Implanter Pen,4 is not yet commercially available.
The Future in Hair Transplantation - NHI
12 of 28
Choi Hair Transplanter
The Choi instrument has, until recently, been the only device in use, which makes the recipient sites and places the grafts
at the same time. However, it holds only one graft at a time and the loading process is laborious, time consuming and
inefficient. It also works best with the more rigid, coarse Asian hair since it pushes (rather than pulls) the hair into the
recipient site. Its advantage over the manual technique is that the manual skills for placing grafts is largely eliminated
refocusing the technical skills to loading the Choi device by hand. However, for a well-trained technician, it can take
longer to load the Choi device than it takes to place grafts by hand. Another advantage is that human variables are
reduced during the placement process.
The Rapid Fire Hair Implanter Carousel™
Like the Choi Device, the Carousel combines what was always a two step process into a one step process but is not
limited to holding and delivering just a single graft. The Carousel uses a cartridge to hold 100 grafts in a controlled
environment. The Choi Device employs a piston and pushes the grafts into the hole while the Carousel gently pulls the
graft into the hole. The author believes that this mechanism is superior to the Choi mechanism as it protects the grafts
from compression during the placement process thereby minimizing trauma. It is also more versatile, easily
accommodating different shaft diameters. The Carousel should provide the following benefits:
1. Single Action for Graft Placement: Each recipient site is created and the graft is placed directly into the recipient
site with a single mechanical action. In the majority of cases, the grafts will remain in place with no additional
manipulation. In certain situations, the grafts may need a fine adjustment to keep them from lifting after insertion.
2. Less Bleeding: Bleeding is reduced in the majority of sites as immediate graft placement compresses many of the
smaller blood vessels in the recipient site. The immediate insertion of the graft creates a tamponading effect on
small open blood vessels.
3. Less Anesthesia Administered: The total anesthesia dosage is reduced commensurate with the shorter surgical
time.
4. Less Graft Manipulation: Manipulation of the grafts during the placement process is virtually eliminated. The
compression (squeezing) of the graft with forceps is no longer necessary for the placement process. This reduces
the possibility of damage to the graft.
5. Controlled Graft Storage: There is no significant period in which the grafts are exposed to the atmosphere after
they are prepared. A specially designed cartridge, which is the storage element for the grafts, keeps them moist in
a saline (or lactated Ringer's) droplet until they are placed into the recipient area. This process prevents the
individual grafts from being touched after they are placed into the cartridge.
6. Less Emphasis for Quality Control Monitoring during Placing: Quality control emphasis involved with human
variables are reduced.
7. Better Graft Accounting: Graft accounting is simplified because the count can be based on the slots filled within
the cartridge and the number of times the device is loaded.
8. Less Staff Stress: The time consuming and laborious process of placing the grafts into holes or slits is reduced.
Staff fatigue and eyestrain are minimized.
9. Appropriate Physician Focus: By reducing the tediousness of hair transplantation the surgeon is able to focus on
the excision of the donor site, the design of the hairline, and the placement of the grafts.
10. Shorter Staff Training: The protracted training period required to teach graft placement is reduced. However, at
least one member of the surgical team must be skilled in manual graft placement techniques in the event grafts are
expelled during the placement process, or other situations that may require manual intervention.
11. Procedure Costs: An expedited surgical procedure frees facility capacity and the physician's time to a significant
degree. Because costs are a critical factor in the decision to elect transplantation as a solution to hair loss,
decreased costs should reduce the threshold for the decision ot have surgery.
The Hair Implanter Pen
The Hair Implanter Pen was developed by Dr. Pascal Boudjema, a brilliant inventor in field of hair transplantation (he also
invented the Calvitron). The Hair Implanter Pen utilizes a suction tip to grasp the end of a hair graft of any small size. The
surgeon drags the graft into a pre-formed wound and then the suction is released along with the graft. As the mechanism
does not grasp or squeeze the graft, there should be little or no trauma to the graft. The Hair Implanter Pen can increase
the placing speed, thereby reducing the surgical time. This instrument should be commercially available in the near
future.
The philosophy that "necessity is the mother of invention" will work to the benefit of both surgeon and patient. Newer
automation technologies are inevitable in view of the problems in delivering today's procedures involving the movement of
large numbers of small grafts. We are moving to an integrated, technically based surgical procedure, less dependent
upon many supportive staff, and less costly to deliver. Traditional surgeons' art is the hub of cosmetic surgery and, as
these new technologies evolve, the cosmetic surgeon will be allowed to focus upon that art in the same vein as the other
traditional surgeries he/she performs regularly.
REFERENCES
The Future in Hair Transplantation - NHI
13 of 28
Bernstein RM, Rassman WR, Szaniawski W, Halperin A: Follicular Transplantation. International Journal of
Aesthetic and Restorative Surgery 1995; 3: 119-132.
Choi YC, Kim JC: Single hair transplantation using Choi hair transplanter. J Dermatol Surg Oncol 1992; 18:
945-948.
Rassman WR, Bernstein RM.: Rapid Fire Hair Implanter Carousel: A new surgical instrument for the automation of
hair transplantation. Dermatologic Surgery 1998; 24: 623-627.
Boudjema P: A new hair graft implanter: The hair implanter pen. Hair Transplant Forum Int 1988; 8(4): 1-4.
Advances in Laser Technology
Two major potential drawbacks of conventional "cold steel" created slit recipient sites that have been voiced are graft
compression and decreased hair density when comparable amounts of donor material are transplanted into recipient sites
in which bald tissue is not removed.1 With "cold steel", whether needle, knife or other sharp instruments, the slit recipient
site represents a stab wound during which the skin merely "pops open", since recipient tissue is not removed. Laser
assisted hair transplantation sought to address these shortcomings. Unfortunately, the "Laser" is often considered
synonymous with the carbon dioxide (CO2) laser, which produces a significant thermal burn in the process of creating the
recipient site. The advantage of the laser's ability to rapidly create uniform recipient sites with less bleeding than
conventional cold steel techniques has been overshadowed by the tissue injury it causes. This article will serve to
introduce the reader to the Erbium: YAG Laser as a new means of creating recipient sites without the thermal
consequences of CO2 lasers.
The carbon dioxide laser was first invented by Bell Laboratories in 1964 and offered the advantage of hemostasis while
"cutting." This laser emits light in the far infrared portion of the electromagnetic spectrum at 10,600 nm, a wavelength that
is highly absorbed by water. Because approximately 70% to 80% of skin tissue is composed of water, this absorption is
nonspecific and is the basis for the use of the CO2 laser as a cutting tool. Cutting is achieved by focusing the CO2 laser
beam to a 0.1 – 0.2-mm spot size, resulting in a focal impact generating temperatures > 300 degrees Celsius at the
immediate zone of injury.2 This results in various zones of thermal damage (burn wound) depending on the laser used.
This burn wound creates a locus minoris resistensiae (an area of decreased resistance) in the skin, the skin "pops open"
about this zone of thermal damage, and minimal amounts of bald tissue, corresponding to the tiny CO2 laser spot sizes
employed, are removed. The spot size was 0.2 mm emitted by one CO2 laser in the creation of slits,1 and a 0.15mm spot
size from another in which punctiform sites were created.3
Equally, if not more importantly, the use of the CO2 laser to create hair transplant recipient sites introduced additional, if
not more, drawbacks than its use was intended to solve. The zone of thermal damage compromises blood flow and
decreases the fibrin network that acts as a "biologic glue" to hold the grafts in place. Not surprisingly, some grafts were
reported to "fall out".4 This zone of thermal damage also compromises the proper oxygenation and nutritive flow to the
grafts, thus compromising graft survival. Moreover, a zone of thermal necrosis during the acute phase of wound healing
must first be removed by the body. This led to reports of impaired graft revascularization, increased inflammation and
prolonged crusting of up to two weeks, delay onset of growth by up to eight weeks, as well as sparse growth and scarring.
3,5,6
Dr. Walter Unger, who has been studying the use of CO2 lasers in hair transplantation since 1993, has generated an
impressive body of work that is admirable for the scientific approach brought to these studies. Because Dr. Unger came to
the conclusion that the cosmetic results were not superior when the Sharplan laser was used, and superior cosmetic
results were inconsistent with the Ultrapulse CO2 Laser (Coherent), this prominent hair transplant surgeon announced in
early 1998 that he had abandoned the use of the CO2 laser for hair transplantation.7
Imagine a technological advance in which bald tissue is actually removed, yet there is no burn at the wound edges to
compromise the building of the fibrin network, the "biological glue" that holds the transplants in place, or compromising
blood flow that delivers the crucial oxygenation and nutritive flow essential for graft survival prior to graft revascularization.
The Erbium: YAG Laser represents such a technological advance. This laser (Er:YAG) has an emission line at 2940nm
coincident with the strongest absorption peak of water (at least ten times greater than CO2!). Equally, if not more
importantly, the Erbium: YAG Laser's wavelength is near a local collagen absorption peak at 3030nm. The result on
impact is much greater precision of tissue removal, almost nonexistent thermal damage, and "actual removal" of tissue!
For example, by using the Erbium:YAG Laser to create 1000 recipient sites we are also now performing 1000 "mini
alopecia reductions", without the longitudinal scars inherent to alopecia reduction surgery. With the 1mm spot size we
have used over the past two years this represents 785mm2 of bald tissue removed (pie r2 = 3.14 x 0.5mm2 x 1000 =
785mm2) per 1000 grafts.
Graft compression is a separate issue we have all at one time or another encountered. When grafts are trimmed to fit into
very small recipient sites ("skinny" grafts"), they may be more subject to injury and, in addition, some telogen hairs may
be trimmed away.8 Importantly, one study showed up to 24%,9 and another presented by Dr. Beehner showed a loss of
up to 33% of hairs,10 when such "skinny" as opposed to "chubby" grafts were prepared. "Skinny" grafts may also result in
finer and frizzy hair growth as opposed to hair growing from "chubby" grafts.10 The advantage of bald tissue removal in
not compressing such "chubby" grafts which also contain viable telogen hairs, as might be the case in a narrow slit,
should be apparent.
The Future in Hair Transplantation - NHI
14 of 28
In the initial studies using an Erbium:YAG Laser (Candela\Fotona) for hair transplantation, a total of 35 laser created
recipient site scalp specimens were evaluated histologically by two "blinded" dermatopathologists. It was shown that, at
the level of the lower reticular dermis and in the fat at the level at which a transplanted follicle would reside, the skin
exhibited 0 to less than 10 microns of thermal damage as measured by an ocular micrometer on a microscope.11,12
An update on the original patient group who underwent hair transplantation with micro- and minigrafting with 2001
recipients sites created by Erbium:YAG Laser alone, and in combination with 1934 "cold steel" created slit recipient
sites12 showed that bleeding from the Erbium:YAG Laser (a "cold laser") created recipient sites was not a clinical
problem and was easily controlled with tumescent local anesthesia. Oozing was similar between the Erbium:YAG Laser
and cold steel created recipient sites and there was no apparent difference in the "take." In addition, unlike the experience
that has been reported with some CO2 laser created recipient sites, no grafts were known to "fall out." Equally important,
because of the similarity between the Erbium:YAG Laser and cold steel, there seemed to be no detectable compromise of
oxygenation and nutritive flow to the grafts, as witnessed by similar "yields" in the growth of the grafts, and no infection or
scarring has, as yet, been noted.
These observations are further underscored by the following: when the Erbium:YAG Laser was used as a "warm" laser to
emulate the properties of a CO2 laser, we did note prolonged crusting by up to five days and a delay in the onset of hair
growth by up to three weeks. An Er:YAG laser functions as a "warm" laser when very high pulse repetition rates are
programmed into the Erbium:YAG Laser's computer. These clinical observations cast strong doubt concerning any
advantage of a recently introduced laser that combines CO2 and Erbium:YAG Laser beams into one. In fact, clinical
experience suggests that the advantages of an Erbium Laser for hair transplantation would be, at least partially,
abrogated utilizing such a device since it would limit the ability to create scalp recipient sites in which our goal is to
preserve graft oxygenation and nutritive flow during one of the follicles' most vulnerable periods.
Although the Erbium:YAG Laser used (Candela\Fotona) created slits, Erbium made slits are cumbersome and
time-consuming to produce with the present technology. This is why circular recipient sites were the ones performed over
the past two years in the majority of patients.
"Nirvana" in Erbium:YAG Laser hair transplantation has not yet been achieved and there have already been exciting
advances since the initial group of patients was treated. Present power outputs from Erbium Lasers are less than ideal,
unnecessarily slowing the procedure while leaving the door open to the inadvertent introduction of unnecessary thermal
damage by laser users turning up the pulse repetition rate in an effort to compensate for the inadequate power output
provided by some Erbium:YAG Laser manufacturers. A new 2500 mJ Erbium:YAG Laser seems to be clinically superior to
the original 1000 mJ output.
It is important for the reader to realize that the beam profile of the laser beam emitted by some laser manufacturers is far
from ideal. Indeed, some beam profiles have been reported to be in the shape of a "doughnut," i.e. the energy is greatest
at the sides with the central area possessing the lowest energy. This is not desired in a beam profile and leads to
markedly increased zones of thermal damage at the wound edges, as has been noted by some investigators using such
lasers.
There are a number of other advances that have recently been introduced. One manufacturer (Dornier Med Tech) already
offers a telescopic handpiece capable of altering the beam diameter with a simple sliding bar built into the handpiece.
Another laser manufacturer (ConBio) offers a variety of 0.5, 0.75 and 1mm spot sizes for use in hair transplantation. Most
importantly, another manufacturer (Dornier Med Tech) is already in the final stages of releasing a "slit hand piece" truly
capable of making slits of various dimensions quickly. This hand piece should be usable with a computer-generated
scanner, as well as manually, to appropriately adapt to many transplant situations.
The ability of the new Erbium: YAG Laser to rapidly create uniform recipient sites, and its ability to create a slit while at the
same time removing recipient tissue without causing significant thermal injury to the recipient bed, represents a significant
advance over CO2 lasers. The Erbium:YAG Laser is an important new addition to the hair transplant surgeon's
armamentarium.
REFERENCES
Unger W.P.: Laser Hair Transplantation IIII. Computer-assisted Laser Transplanting. Dermatol Surg 1995; 21:
1047-1055.
Nemeth A.J.: Lasers and Wound Healing. In: Nemeth A.J. (ed.): Dermatologic Clinics – Wound Healing. W.B.
Saunders Co. Vol. II No. 4; 1993, pp 783-789.
Villnow M.M., Fenduni B: Update on Laser-assisted Hair Transplantation. Dermatol Surg 1998; 24: 749-754.
Bernstein R.J., Rassman W.: Laser Hair Transplantation: Is It Really State of the Art? Lasers Surg Med 1996; 19:
233-238.
Fitzpatrick R.E.: Laser Hair Transplantation. Tissue Effects of Laser Parameters. Dermatol Surg 1995; 21:
1042-1046.
Unger WP: Update On Lasers. Hair Transplant Forum Intl. 1997; 7(2): 19
Unger WP: Presentation on Laser and Controversial Hair Transplantation. Am Soc for Dermatol Surg in Portland,
Oregon, May 13-17, 1998.
The Future in Hair Transplantation - NHI
ISHRS Washington D.C. September 16-20, 1998
Seager D.J.: Micrograft Size and Subsequent Survival. Dermatol Surg 1997; 23: 757-761
Beehner M.: Two Research Studies on Follicular Unit Growth. ISHRS in Washington, D.C. September 16-20, 1998
Nemeth A.J., Miller I, Messina J.L., Glass F, Rehnke R.D: Erbium:YAG Laser-assisted Hair Transplantation: A
Clinical and Histological Study. ISHRS in Barcelona, Spain, October 15-19, 1997.
Nemeth A.J.: Erbium Laser Hair Transplantation: Update and Present Status. ISHRS in Washington, D.C.,
September 16-20, 1998
COMMENTARY
There is no doubt that the new Erbium: YAG Laser offers substantial improvement over traditional CO2 lasers in
eliminating thermal injury. For those practitioners who use minigrafts and larger grafts containing multiple follicular units,
the ability to rapidly create recipient slits and cause less graft compression, is a significant advantage. For those of us
who use individual follicular units to keep the wound sizes to a minimum, the usefulness of the laser is less obvious. It is a
concern to some of these authors that the wounding produced when recipient tissue is removed is not equivalent to a
small "cold steel"slit. Well controlled studies are much needed to resolve this important issue.
Robert M. Bernstein, MD
Splitting Hairs
Not a hair transplant procedure is performed without at least implanting a few transected follicles. What happens if grafts
with transected follicles are planted?
To answer this question, a study was performed in which excised skin from the human occipital scalp was cut by a
surgical blade along the direction of hair growth. Intact individual human anagen hair follicles were isolated with a scalpel.
Implants were prepared from follicles as follows:
The upper one-third and lower two-thirds of the follicle were obtained by horizontal section just below the
pilo-sebaceous junction.
The upper and lower halves of the follicle were obtained from a transverse cut at the middle portion of the follicle
The upper two-thirds and lower one-third of the follicle were obtained from the transection of the follicle at the lower
one-third of the follicle.
Both upper and lower follicle grafts were transplanted onto the forehead or leg. Histologic examinations were performed
for each successive biopsy after grafting. Lower half follicles and intact (non-transected) follicles were cultured in
Philpott's medium1. Follicles were measured daily using inverted microscopes with a calibrated eyepiece graticule.
Eight months after grafting, 13 of the 20 grafted upper two-thirds, 25 of the 30 grafted lower two-thirds, 10 of the 25
grafted upper half, and 4 of the 15 lower half follicles have regenerated complete hair follicles. However, no hair follicles
were regenerated from the grafted lower one-third and upper one-third follicles. The regenerated hairs from upper follicle
implants were thinner than those from lower follicle implants.
A histologic examination showed that the regenerated hair follicle from the upper half follicle implant revealed the
presence of a reformed small dermal papilla and a matrix. Lower half follicle implants reconstituted the complete hair
follicle. Sebaceous glands were also completely regenerated. Some lower half grafts formed epithelial cysts.
Dissected hair follicles will grow and retain their morphology for 8 days in culture. Intact follicles show prominent naked
shaft outgrowth. In contrast, the outer and inner root sheath grows concomitantly with the shaft in lower half follicles (1.5
mm after 8 days).
The results of this study showed that if the bulb containing the dermal papilla is removed, the hair will usually regrow. If
the papilla is necessary for hair growth, how will hair regrow without it? A new papilla appears to be reformed from the
connective tissue sheath2. However, the higher up in the follicle that transection occurs, the smaller will be the papilla that
is reformed and hence the smaller and finer the hair is which is produced. The papilla determines the caliber of the hair
shaft3. And if transection occurs above the midpoint of the follicle, a new papilla is not formed and hence no hair grows.
Thus, loss of the bulb region during graft dissection and placement is a clinically significant problem, which can contribute
to incomplete and fine hair growth. However, this problem may be useful for the eyebrows, pubic hair, and female hairline
reconstruction. In contrast to males, the female hairline is generally made up of fine vellus hairs that give it its "soft"
character. One can successfully graft single hair follicles after removal of the bulb for the reconstruction of these regions.
This technique can provide the best possible cosmetic result.
If the follicle is transected in its upper portion and is planted so that it is stranded in the dermis, cyst formation is likely4.
Our results showed that some grafts formed epithelial cysts, but 25 of the 30 grafted lower two-thirds and 4 of 15 lower
half follicles regenerated complete hair follicles. The sheath components grew out at the same rate as the shaft (1.5 mm
for 8 days) in culture. This result suggests that the outer and inner root sheath grew out and could connect with epidermal
invagination in vivo. If grafted hair follicles were located too deep, the re-grown sheath could not reach the epidermal
15 of 28
The Future in Hair Transplantation - NHI
16 of 28
layer. In this situation, the formation of an epidermal cyst is likely.
REFERENCES
Philpott MP, Kealey T. Effects of EGF on the morphology and patterns of DNA synthesis in isolated human hair
follicles. J Invest Dermatol 1994;102:186-191.
Kim JC, Choi YC. Regrowth of grafted human scalp hair after removal of the bulb. Dermatol Surg
1995;21:312-313.
Oliver RF. Whisker growth after removal of the dermal papilla and lengths of follicle in the hooded rat. J Embryol
Exp Morphol 1966;15:331-347.
Cooley J. Rat whiskers, follicle transection, and hair transplantation. Hair Transplant Forum 1997;7(2):20-21.
The Future in Graft Storage
When performing hair transplantation procedures, it is of the utmost importance to try to obtain the maximum survival rate
possible of transplanted micrografts. Although numerous factors (such as dehydration of grafts, trauma in handling with
forceps, etc.) play a critical role in the graft survival, a "metabolic pre-conditioning" of hair grafts by means of dedicated
storage mediums should have value in striving to enhance the survival rate of grafts when performing hair transplantation
surgery.
Knowing the best way to preserve the grafts is particularly important with the advent of megasessions (involving the
transplant of a large number of very small grafts), since a significant period of time may elapse between graft harvesting
and their implantation in the recipient area. At present, it is generally recommended to preserve the grafts at a low
temperature (1ºC - 4ºC), in order to enhance the survival rate of the grafted hairs1. Indeed, it is assumed that, as in other
major transplant procedures, lowering the metabolism of the grafts by means of a reduction of their temperature may be
of some utility for enhancing their survival rate. On the other hand, since the development of tissue preservation regimes
has achieved great successes in the preservation of vital organs and grafts in the interval between harvest and
re-plantation into the recipient area, other additional methods should be considered.
In this regard, for example, the role of oxygen free radicals in tissue ischemia has been well documented. Oxygen free
radicals in ischemic tissue are generated from a number of different sources. The relative importance of these
mechanisms is not known. It would follow, however, that the prevention of action of radicals produced by all of these
pathways would be more effective in preventing tissue damage than by blocking the radicals produced by a solitary
pathway2. Similarly, analysis of cellular metabolism in hypoxic conditions reveals not only an accumulation of cytotoxic
metabolites, but also a gradual depletion of cellular energy stores3.
Increased intracellular use of high-energy adenosine triphosphate (ATP) and decreased mitochondrial regeneration of
ATP occur under anaerobic conditions3-6. These changes lead to the deterioration of normal cellular processes and
eventual cellular demise.
The above-mentioned considerations can be can applied to the field of hair transplantation surgery. Deferoxamine has
been shown2 to be a potent, non-selective scavenger of oxygen free radicals, while exogenous ATP is thought to
replenish depleted intracellular ATP, since several observations support the notion of intracellular uptake of extracellular
ATP by ischemic cells. Indeed, addition of the exogenous high-energy cellular substrate adenosine triphosphatemagnesium chloride has been shown to substantially improve cellular preservation and tissue viability in ischemic
conditions6.
In a recent study7, normal human occipital scalp samples were obtained, from ten healthy male patients, during routine
excision of benign scalp lesions. Isolation of anagen hair follicles was achieved by stereo-microscopic dissection. A total
of 200 anagen hair follicles (20 follicles per each sample) were obtained.
Follicles from each of the ten occipital scalp samples were thus randomly assigned to one of the following group: Group A
(control; n=10 follicles per each scalp sample; total n=100 follicles), and Group B (experimental; n=10 follicles per each
scalp sample; total n=100 follicles). While follicles from Group A were preserved, for five hours, in a Petri dish filled with
isotonic saline, follicles from Group B were preserved, for five hours, in a Petri dish filled with saline containing adenosine
triphosphate-magnesium chloride 0.1 µmol/ml and deferoxamine mesylate 15 mg/ml.
Immediately after the five-hour period, hair follicles from both Groups were stored in 500 ml of Williams E medium with
supplements as follows: 1% fetal calf serum, 10 mg/ml transferrin, 10 mg/ml insulin, 10 ng/ml sodium selenite, 10 ng/ml
hydrocortisone, 100 U/ml penicillin, 100 mg/ml streptomycin, 2.5 mg/ml fungizone, and cultured for ten days8. Follicles
were maintained free floating in individual wells of 24-well multi-well plates in an atmosphere of 37ºC, 5% CO2 - 95% air,
and 100% humidity. This has permitted detailed measurements to be made on both the length and survival rates of the
tested follicles.
The length of each follicle was measured at magnification x20 immediately following the five-hour test period and at the
end of the ten-day culture period, using a calibrated microscope. Total follicle length was computed as the distance from
the base of the bulb to the end of the shaft. Follicles which lost normal follicular architecture due to degeneration late in
the culture period were computed as not survived. Histology was accomplished, at the end of the ten-day culture period.9
The Future in Hair Transplantation - NHI
17 of 28
Most of the dissected follicles grew and retained their morphology for the whole ten-day period of culture.
A statistically significant difference was found between the survival rate (considered as preservation of normal follicular
architecture and absence of degenerative signs) of follicles from the Control Group (87%) and Experimental Group (98%).
Photographs taken of freshly isolated and maintained hair follicles showed that the increase in length over ten days was
not associated with any disruption of hair follicle architecture. The length increase always occurred by the production of
keratinized hair shaft. All the survived follicles produced a measurable shaft elongation, and no statistically significant
differences were found between the growth rate of follicles from the Control and the Experimental groups. Histologic
analysis demonstrated that the survived follicles from both Groups always maintained a normal histologic appearance,
even after 10 days in culture.
The reported study addressed the question of whether an "enhanced" preservation solution, containing adenosine
triphosphate-magnesium chloride and deferoxamine mesylate, is suitable for preservation of hair grafts, and whether this
pharmacological/metabolic treatment may further enhance viability of transplanted micrografts. The survival rate of
follicles from the control Group was consistent with that reported by Limmer10, storing the grafts in chilled isotonic saline
at 4ºC. Conversely, our experimental data were indicative of a significant increase in the survival rate of hair micrografts
pre-treated with adenosine triphosphate-magnesium chloride and deferoxamine mesylate.
In conclusion, it should be taken into account that the study discussed was just an in vitro study, and that the obtained
results should be validated by further in vivo studies. Similarly, further studies need also to be undertaken in order to
evaluate and compare other storage mediums. As hair transplant procedures continue to increase in length, metabolic
pre-conditioning of hair grafts should play an important role in ensuring maximum follicular survival.
REFERENCES
Fan J, Raposio E, Nordström REA: Minigraft preparation in surgical hair replacement. Scand J Plast Reconstr
Hand Surg 1997; 31: 83-7.
Kohout M, Lepore A, Knight KR, et al.: Cool perfusion solutions for skin flaps: A new mixture of pharmacological
agents which improves skin flap viability. Br J Plast Surg 1995; 48: 132-44.
Zimmerman TJ, Sasaki GH, Khattab S.: Improved ischemic island skin flap survival with continuous intraarterial
infusion of adenosine triphosphate-magnesium chloride and superoxide dismutase: A rat model. Ann Plast Surg
1987; 18: 218-23.
Machiedo GW, Ghuman S, Rush BF, et al.: The effect of ATP-MgCl2 infusion on hepatic cell permeability and
metabolism after hemorrhagic shock. Surgery 1981; 90: 328-32.
Maxild J.: Effect of externally added ATP and related compounds on active transport of p-aminohippurate and
metabolism in cortical slices of rabbit kidney. Arch Int Physiol Biochim 1978; 86: 509-14.
Williams D, Reibel DK, Rovetto MJ.: ATP induced increase in ATP content in cultured myocardial cells. Fed Proc
1979; 38: 1389-93.
Raposio E, Cella A, Panarese P, Nordström REA, Santi PL.: Power-boosting the grafts in hair transplantation
surgery: Evaluation of a new storage medium. Dermatol Surg (in press).
Raposio E, Filippi F, Levi G, Nordström REA, Santi PL.: Follicular bisection in hair transplantation surgery: An in
vitro model. Plast Reconstr Surg 1998; 102 (in press).
Heidenhein M.: Uber die Maliorysche Bindegeweosfarbung mit Karmin und Azokarmin als Vorfarben. Ztsch F
Wissensch Wikr 1915; 32: 361-4.
Limmer BL: Micrografts survival. In: Stough DB, ed. Hair Replacement: Surgical and Medical. St. Louis: Mosby
Press 1996: 147-9.
The Future Of Wound Care
Wound healing involves a coordinated series of events involving specialized cells, polypeptide growth factors, proteinases
and proteinase inhibitors, as well as nutritional factors. Initially after a wound is created, the body seals off or reduces
blood flow into the area and neutrophils migrate to the site to secrete toxic superoxide and other highly reactive molecules
to sterilize and induce a general inflammation.
In the next phase of healing, this inflammatory response is suppressed while macrophages and fibroblasts migrate into
the injury to secrete specific growth factors and to begin the process of rebuilding tissue. The fibroblasts are stimulated to
produce new collagen, proteoglycans and other extracellular matrix components, and new blood vessels are formed by
capillary endothelial cells.
Non-viable tissue is removed, cell migration and new blood vessel formation are facilitated, and remodeling is
accomplished through the action of specific proteinases (MMP or matix metalloproteinase). These proteinases are
controlled through the action of specific inhibitors (TIMP or tissue inhibitor of metalloproteinase). Overall, many of the
activities involved in wound healing have been shown to be controlled by specific growth factors secreted by cells
involved in the process or liberated during the early stages of clot formation.
THE PRESENT
The modern wound healing theory is that optimal healing is based on maintaining a moist wound environment containing
The Future in Hair Transplantation - NHI
all the factors necessary for healing to proceed. The purpose of a wound dressing is to provide a protective environment
for tissue healing. An optimal wound dressing should:1
Maintain the proper humidity at the wound surface
Control fluid (wound exudate)
Be easy to apply and remove
Allow air and water vapor to escape or enter
Provide thermal insulation
Provide a barrier to contamination
Be non-toxic
Conform to the wound surface
Modern wound care practices aim to optimize wound healing through the use of select nutritional and growth factors
which bring an additional trait for an optimal wound dressing.
Provide an enriched wound environment
Wound dressings used for acute and chronic wound care consist of a wide range of natural and synthetic materials2,3 .
These dressings, used singly or in combinations, can provide many of the characteristics of optimum wound dressings in
terms of protection of the wound from contamination and management of wound fluids.
In addition to the management of wound fluid and contamination, many modern wound dressings are developed to create
an environment to optimize wound healing underneath the dressing. This is accomplished through the application of
nutritional factors such as copper and zinc, botanicals such as aloe vera, and sterilants or odor control agents. For
example, the combination of moisture management and nutrient copper supplementation in the form of the GraftCyteÔ
product line became available for cosmetic and dermatological wound care in 1997.
Tissue glues have received considerable interest as a speedy and safe equivalent to sutures. In the studies reported,
their use resulted in significantly quicker closure with equivalent cosmetic results to traditional sutures9-13.
The importance of growth factors to wound healing has been discussed above and a number of factors (epidermal growth
factor (EGF), transforming growth factor (TGF), and platelet derived growth factor (PDGF)) have been the subject of
intensive investigation16-18. 1998 saw the introduction of a long awaited growth factor product in the wound care field.
This was the first commercially available human growth factor (PDGF, Regranex® Gel, J&J) which was approved by the
FDA for topical application to chronic wounds.
THE FUTURE
What might the future practice of wound care involve? Integration of the protective and fluid handling properties of
modern synthetic dressings with direct application of factors to enhance the wound environment is the most likely
scenario. These "interactive" dressings and treatments would allow the physician to intervene in a positive and stimulatory
way in the healing process rather than just protecting the wound and letting nature take its course.
The recent approval of Regranex® Gel provides the first commercially available product to allow the practicing clinician to
supplement the wound with a natural factor, which initiates and ultimately controls part of the process. The increasing
availability of dressings and treatments which provide micronutrients and other factors will help provide the building
blocks and cellular tools to further enhance wound healing.
One of the most exciting approaches to manipulation of the wound healing process involves the application of modern
molecular biology techniques to the proven participation of growth factors in the healing process. There are several
approaches to the addition of growth factors to damaged tissue involving genetic technology. This can be through either
the genetic modification of cells and their subsequent introduction to the wound or direct in vivo introduction of the genes
to the wound. Genetic methodology has the advantage that a constant, regulated source of the growth factors will result.
Skin is an ideal target organ for genetically modified cells, as the turn over of skin cells will eliminate the modified cells as
part of the normal healing process. Genetically modified keratinocytes have been prepared by the insertion of a plasmid
containing the TGFb 1 or EGF gene. These genetically modified keratinocytes were shown to release high levels of the
corresponding growth factor to wounds19,20. In a similar manner, genetically modified human keratinocytes
over-expressing PDGF-AA were used as the epidermal part of a composite skin graft. The composite graft composed of
the genetically modified keratinocytes performed significantly better than control grafts in an animal model21.
Direct transfection with genes coding for growth factors is also a promising therapy. Topical application or transfection with
a plasmid containing the gene for aFGF has been shown to significantly increase the closure and breaking strength of
experimental wound 22 as has particle transfer of the human EGF gene23.
The entry to the field of artificial human skin is another promising technology to be applied to dermatology and cosmetic
surgery. These products hold the promise of an unlimited source of replacement skin (full or partial thickness) for
reconstructive and cosmetic purposes. No longer will skin have to be recycled from another site nor will the clinician and
18 of 28
The Future in Hair Transplantation - NHI
19 of 28
patient have to wait for new skin to cover a defect. Additional advantages of these products is that they serve an
additional role as "biological" bandages which possess many of the attributes of an optimum wound dressing. Of course,
the obvious combination of genetically modified cellular components to artificial skin replacements brings together the
ability to manipulate the healing process with the instant coverage provided by artificial skin.
All wound healing consists of an integrated sequence of events involving specialized cells, growth factors, proteinases
and proteinase inhibitors, and nutritional factors. Current medical practice for wound care is based on maintaining a
protected moist wound environment. Future directions for wound care will be based on the ability to manipulate the
wound environment with micronutrients, growth factors, and living cells. These enhanced wound care strategies should
lead to faster and more aesthetically pleasing results in our hair transplants, in both the donor and recipient areas.
REFERENCES
Szycher M, Lee SJ.: Modern wound dressings: a systematic approach to wound healing. J Biomater Appl 1992; 7:
142-213.
Hanna JR, Giacopelli JA.: A Review of Wound Healing and Wound Dressing Products. The Journal of Foot and
Ankle Surgery 1997; 36: 2-14.
Hess CT.: Wound Care Products: A Directory. Ostomy/Wound Management 1994; 40: 70-94.
Williams R, L, Armstrong D, G.: Wound healing . New modalities for a new millennium. Clinics In Podiatric
Medicine And Surgery 1998; 15: 117-28.
Falanga V, Margolis D, Alvarez O, Auletta M, Maggiacomo F, Altman M, et al.: Rapid healing of venous ulcers and
lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators
Group [see comments]. Archives Of Dermatology 1998; 134: 293-300.
Sorensen J, C.: Living skin equivalents and their application in wound healing. Clinics In Podiatric Medicine And
Surgery 1998; 15: 129-37.
Duinslaeger L, A, Verbeken G, Vanhalle S, Vanderkelen A.: Cultured allogeneic keratinocyte sheets accelerate
healing compared to Op-site treatment of donor sites in burns. Journal Of Burn Care And Rehabilitation 1997; 18:
545-51.
Elson ML. Soft Tissue Augmentation with Allogeneic Human Tissue Matrix. Cosmetic Dermatology 1998; 11:
24-28.
Shigemitsu T, Majima Y.: The utilization of a biological adhesive for wound treatment: comparison of suture,
self-sealing sutureless and cyanoacrylate closure in the tensile strength test. International Ophthalmology 1996;
20: 323-8.
Singer A, J, Hollander J, E, Valentine S, M, Turque T, W, McCuskey C, F, Quinn J, V.: Prospective, randomized,
controlled trial of tissue adhesive (2-octylcyanoacrylate) vs standard wound closure techniques for laceration
repair. Stony Brook Octylcyanoacrylate Study Group. Academic Emergency Medicine 1998; 5: 94-9.
Qureshi A, Drew P, J, Duthie G, S, Roberts A, C, Monson J, R.: n-Butyl cyanoacrylate adhesive for skin closure of
abdominal wounds: preliminary results. Annals Of The Royal College Of Surgeons Of England 1997; 79: 414-5.
Quinn J, Wells G, Sutcliffe T, Jarmuske M, Maw J, Stiell I, et al.: A randomized trial comparing octylcyanoacrylate
tissue adhesive and sutures in the management of lacerations [see comments]. JAMA 1997; 277: 1527-30.
Maw J, L, Quinn J, V, Wells G, A, Ducic Y, Odell P, F, Lamothe A, et al.: A prospective comparison of
octylcyanoacrylate tissue adhesive and suture for the closure of head and neck incisions. Journal Of
Otolaryngology 1997; 26: 26-30.
Mendez-Eastman S.: Negative pressure wound therapy. Plastic Surgical Nursing 1998; 18: 27-9, 33-7.
Genecov D, G, Schneider A, M, Morykwas M, J, Parker D, White W, L, Argenta L, C.: A controlled subatmospheric
pressure dressing increases the rate of skin graft donor site reepithelialization. Annals Of Plastic Surgery 1998; 40:
219-25.
Robinson C, J.: Growth factors: therapeutic advances in wound healing. Annals Of Medicine 1993; 25: 535-8.
Falanga V.: Growth factors and wound healing. Dermatologic Clinics 1993; 11: 667-75.
Meyer-Ingold W.: Wound therapy: growth factors as agents to promote healing. Trends In Biotechnology 1993; 11:
387-92.
Ghahary A, Tredget E, E, Chang L, J, Scott P, G, Shen Q.: Genetically modified dermal keratinocytes express high
levels of transforming growth factor-beta1. Journal Of Investigative Dermatology 1998; 110: 800-5.
Rosenthal F, M, Cao L, Tanczos E, Kopp J, Andree C, Stark G, B, et al.: Paracrine stimulation of keratinocytes in
vitro and continuous delivery of epidermal growth factor to wounds in vivo by genetically modified fibroblasts
transfected with a novel chimeric construct. In Vivo 1997; 11: 201-8.
Eming S, A, Medalie D, A, Tompkins R, G, Yarmush M, L, Morgan J, R.: Genetically modified human keratinocytes
overexpressing PDGF-A enhance the performance of a composite skin graft. Human Gene Therapy 1998; 9:
529-39.
Sun L, Xu L, Chang H, Henry F, A, Miller R, M, Harmon J, M, et al.: Transfection with aFGF cDNA improves wound
healing. Journal Of Investigative Dermatology 1997; 108: 313-8.
Andree C, Swain W, F, Page C, P, Macklin M, D, Slama J, Hatzis D, et al.: In vivo transfer and expression of a
human epidermal growth factor gene accelerates wound repair. Proceedings Of The National Academy Of
Sciences Of The United States Of America 1994; 91: 12188-92.
New Medicines as an Adjunct to Surgery
The Future in Hair Transplantation - NHI
The search for new and effective agents to treat many different hair loss problems has been intensified by the increase in
hair biology research taking place worldwide, from university-academic institutions to the pharmaceutical companies, all
with a desire to profit from marketing such drugs which have been termed, "cosmeceuticals." Millions of men and women
of every race suffer from various forms of alopecia, the most common being AGA, where DHT aggravates genetically
programmed scalp hair follicles, resulting in short, fine, miniaturized hairs.
There is a great need for drug therapies which specifically attack the metabolic pathways involved in the balding process.
This section will describe the most recently approved products for AGA, along with some in clinical trial development that
may be used either alone or as an adjunct to surgical interventions.1
5a-REDUCTASE INHIBITORS
In this category there are the structural steroid competitive inhibitors that chemically resemble the substrate, testosterone,
and bind to the active site of the enzyme so that DHT is not formed. Propecia (finasteride) has recently been FDA
approved in the USA for men with AGA. Propecia is a specific 5a-reductase type II enzyme inhibitor, and does not bind to
the AR, and is therefore not called an "anti-androgen", but an androgen inhibitor.
The pharmokinetics of finasteride reveal that after a 1 mg dose serum concentration of DHT decreases by 65% in 24
hours. Serum concentrations of testosterone and estradiol increase about 15% but remain within normal limits. Prostate
concentrations of testosterone increase about sixfold2. Finasteride is well absorbed in the GI tract, metabolized in the
liver and excreted in urine and feces, with a half-life of 5 to 6 hours. Small nanogram levels of the drug are detectable in
human semen, but are not thought to have any consequence in women who are exposed by sexual contact.
Three double-blind multi-center trials were conducted in men ages 18 to 41 years and the results of these trials have
been presented as abstracts3,4. In combined results from two of the trials, 1553 men with mild to moderate male AGA of
the vertex took finasteride 1 mg/day or a placebo orally for one year. After three months of treatment, the men who took
finasteride were more satisfied with the appearance of their hair. At the end of 1 year, in a circle on the vertex scalp, a one
inch diameter mean baseline hair count was 876. Patients who took the drug had an average of 107 more hairs than
those who took the placebo. Hair counts were maintained for up to 24 months in the men who continued to take the
drug4. A third study in 326 men with mild to moderate frontal hair loss found that after one year, finasteride treated men
had statistically significantly higher hair counts in their frontal scalp. Approximately 50% of treated men and 30% of those
who took placebo thought the appearance of their hair had improved. Hair regrowth was not reported in older men taking
5 mg finasteride (Proscar), perhaps because it was not indicated in those trials to make observations on the scalp.
Adverse events described with 5 mg finasteride (Proscar) in a small percent of older men were loss of: libido and
erection, ejaculatory dysfunction, hypersensitivity reactions, gynecomastia and severe myopathy2. Finasteride 1mg
causes a 30 to 50% decrease in prostate specific antigen (PSA) in clinical trials in men 18 to 41 years old. The decreased
libido, erectile dysfunction or a decreased volume of ejaculate have been reported in less than 2% of patients, which in
reality is between 0.5% to 1% when compared against placebo and these effects are reversible when the drug is
discontinued.
Finasteride has teratogenic effects in animals when taken in high doses, causing genitourinary abnormalities in male
offspring. The concentration of the drug in semen of men who took 1 mg/day was much lower than the concentration
associated with teratogenic effects in monkeys. Merck warns that women who are, or who may become pregnant should
not have exposure to finasteride orally or by exposure of handling crushed or broken tablets, due to possible adverse
effects on the male fetus. Finasteride is not indicated for use in women at the present time. There have been no published
benefits for the use of finasteride in post-menopausal women thus far.
Dutasteride (GI198745, GlaxoWellcome) is a dual 5a-reductase inhibitor blocking both type I and II isoenzymes, which is
currently in clinical trial studies around the USA for males with AGA. It is structurally similar to the parent structure of
finasteride, maintaining the 4-aza structure of the steroid nucleus. However on the 21-carbon position is a tri-fluorophenyl
group which renders the molecule to be electronegative and perhaps gives it greater affinity for both the type I and II
isoenzyme forms of 5a-reductase5. Therefore, this drug is similar to finasteride in structure, but different in that it
competitively inhibits both forms of the 5a-reductase type I and II isoenzymes, whereas, finasteride is just specific for
inhibiting type II 5a-reductase. Dutasteride is known to inhibit >90% serum DHT levels in 24 hours after oral
administration, and because of this greater ability to inhibit DHT, it is thought that it may be more effective in promoting
hair growth, as well as treating acne. The results of clinical trials are pending.
VASCULAR/ANGIOGENIC RELATED COMPOUNDS
Regaine/Rogaine (minoxidil) 2% has been used worldwide for over 10 years, and is now over the counter (OTC) in the
USA. Most recently, Extra Strength 5% Rogaine has hit the OTC shelves in the USA, with approval in November 1997.
Pharmacia-Upjohn has sole rights to being the only manufacturer for the next 3 years for this new version of minoxidil,
which is indicated only for men.
Despite lack of understanding of the distinct mechanism of action, in women it has been shown to increase the non-vellus
hairs when using it for 32 weeks or more2. One potential drawback to minoxidil therapy is that spontaneous reversal to
20 of 28
The Future in Hair Transplantation - NHI
21 of 28
the pretreatment state that can be expected one to three months after cessation of therapy, indicating minoxidil has a
direct effect on the hair follicle, sensitizing it and making it dependent on the drug for future growth. The mechanism of
action although still unclear, seems to open potassium channels and increases proliferation and differentiation of epithelial
cells in the hair shaft2.
Serum concentrations after topical application of 2% minoxidil, used twice a day are generally about 5% of those with oral
minoxidil, and with the 5% solution they are about 10% of those treated with the oral drug. Minoxidil is metabolized in the
liver and excreted in the urine.
With respect to effectiveness, four unpublished 32 to 48 week studies presented to the FDA compared the effects of
placebo, 2% minoxidil and 5% minoxidil by counting the net gain in hairs in 1 cm2 areas of the scalp. As described2, two
studies in women did not find statistically significant differences between 2% and 5% minoxidil. A 32-week study in men
found that the mean increase from baseline in hairs/cm2 was 5 with placebo, 30 with 2% minoxidil and 39 with 5%
minoxidil. A 48-week study in men found a mean increase in hairs/cm2 of 3.9 with placebo, 12.7 with 2% minoxidil and
18.5 with 5% minoxidil. Previous studies have shown that when the drug is stopped, all of the newly regrown hair falls
out6. Despite these reports the new advertisements claim 45% more effective hair growth than regular strength 2%, with
regrowth occurring as early as 2 months with overall 5 times more hair regrowth than placebo, with no major safety
concerns.
Most physicians and lay people who have been using minoxidil for many years are not concerned about safety aspects,
since most feel it to be a very safe product. Concerns are more on the "effectiveness" of the product in promoting and
maintaining hair growth. The new 5% Extra Strength brings about a new glimmer of hope in showing improved hair
growth for individuals that may not have seen results with 2% minoxidil.
Adverse effects noted with oral minoxidil include tachycardia, angina pectoris and fluid retention. When taken orally during
pregnancy, minoxidil has been associated with hypertrichosis of the fetus and congenital anomalies. One double blind
study in 35 balding men found that topical use of 2% minoxidil caused small but statistically significant increases in left
ventricular end-diastolic volume, cardiac output and left ventricular mass2. Infrequently, dizziness and tachycardia have
been reported with 2% solution, with advice given to patients to reduce frequency of application which helps in eliminating
these side effects. Local irritation, itching, dryness and erythema may occur with the use of topical minoxidil, most likely
due to the vehicle formulation of alcohol and propylene glycol.
The conclusion on minoxidil 5% and 2% solutions are that they can produce a modest increase in hair on scalps of young
men with mild to moderate hair loss, with continuous application for years to maintain the effect. Questions as to use of
5% Extra Strength in women are being posed, with some clinicians already giving this to young women with early hair
loss, even though it is only indicated by the manufacturer Pharmacia-Upjohn for use in men.
Many patients may be asking their physicians now and in the future about using both topical Extra Strength 5% Rogaine
along with oral 1 mg Propecia, which many believe may be beneficial working together synergistically, however further
human clinical trials are needed to verify this, since the only previous study was performed in the Macaque monkey
model, which did show benefit when used together7.
Although other vasodilatory/angiogenic related compounds are progressing through the development pipeline1, it is
difficult to ascertain their effectiveness until human clinical trials are performed. Many compounds that mimic minoxidil in
vasodilatory properties, fail to show the same results, hence there may still be a unique mode of action about this
compound that is yet to be fully uncovered. Unpublished investigations have suggested minoxidil to have oxidativereductive potential to facilitate cofactor reactions necessary in side chain steps for hair follicle growth, as well as other
suggestions of stimulating some of the keratin genes of hair matrix cells for synthesis of hair shaft keratins, producing
thin, fine, indeterminate hairs, often seen with continued use of minoxidil.
MEDICATIONS AS AN ADJUVENT TO SURGERY
Currently available medications should prove to be useful adjuncts to surgical hair restoration for a number of reasons.
Medications work best in the younger patient who may not yet be a candidate for hair transplantation.
Medications are less effective in the front part of the scalp, the area where surgical hair restoration can offer the
greatest cosmetic improvement.
Medications can regrow, or stabilize hair loss, in the back part of the scalp where hair transplantation may not always
be indicated.
Although medications are of little use in patients who have extensive baldness, these patients are often ideal
candidates for hair transplantation.
If medications are shown to be safe and effective in the long-term, they will allow the hair restoration surgeon the
ability to creat more density in the needed areas (such as the frontal hairline), since keeping reserves for future hair loss
will be less of a concern.
With different medical options now available, patients must be educated as to their choices, advised as to how these
agents work, educated to the fact that these drugs need to be used continuously throughout life in order to be of benefit,
and be aware that long-term risks are not yet known. Most importantly, they must be provided with realistic expectations
The Future in Hair Transplantation - NHI
regarding the inability, at the present time, for medications to regrow substantial amounts of hair in the average patient.
As newer, more effective agents are developed, it is certain that they will play a more expanded role in the hair restoration
process.
REFERENCES
Sawaya ME: Alopecia - the search for novel agents continues. Expert Opinion in Therapeutic Patents
7(8):859-872, 1997.
Abramowicz M (Ed): Propecia and Rogaine Extra Strength for alopecia, In: The Medical Letter 40(1021):25-27,
1998.
Kaufman K: Clinical studies on effects of oral finasteride, a type 2 5a-reductase inhibitor on scalp hair in men with
male pattern baldness. Proceedings from First Tricontinental Meeting of Hair Research Societies 1995.
Kaufman K: Updates of clinical phase III trial data and results presented at the American Academy Dermatology
Meeting, San Francisco, CA, March 1997, as well as the World Congress Meeting, Australia, June 1997.
Bramson HN, Hermann D, Batchelor KW, ET AL: The unique preclinical characteristics of GG745, a potent dual
inhibitor of 5AR. J Pharmacotics and Experimental Therapy, 1997.
Kidwai BJ, George M: Hair loss and minoxidil withdrawal. Lancet 340:609-610, 1992.
Diani AR, Mulholland MJ, Shull KL, et al: Hair growth effects of oral administration of finasteride, a steroid 5-alpha
reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque. J Clin
Endocrinol Metab 74(2):345-350, 1992.
Cloning
In August 1967, R.F. Oliver published a paper titled The Experimental Induction of Whisker Growth in the Hooded Rat by
Implantation of Dermal Papillae1, in which he described - as the title implies - the growth of a whisker hair from the
implantation of only dermal papillae cells. Prior to this paper he had demonstrated that implantation of the lower third of
the vibrissa follicle wall would produce a hair, but the implantation of the upper two thirds of the follicle would not2. The
August 1967 report took the study one step further by showing that even the lower third of the follicle was unnecessary
and that dermal papilla cells alone were sufficient to produce hair growth. Other authors have shown that there is an
inductive role of the dermal papilla during the ontogeny of pillage and vibrisae follicles3.
The implications of these results in rats, with regard to human subjects with Male Pattern Baldness (MPB), can easily be
discerned. If we were able to culture human dermal papilla cells (DPC) from a "permanent" hair-bearing donor area in a
patient with MPB, and implant them into the bald area of the same patient and grow hair, we could potentially have an
unlimited supply of donor hair with which to treat that patient. Thus any hair density and coverage would be made
possible in any patient after harvesting a single small piece of donor skin.
With cloning, those portions of hair transplant surgery during which donor tissue is anesthetized, excised, and divided into
grafts would no longer be necessary. In addition, the handling of donor tissue during sectioning and insertion into the
recipient area that can potentially result in decreased hair survival, could be reduced or eliminated. In effect, many of the
time consuming, skill dependent, potentially damaging and costly aspects of hair transplanting could be avoided if a
technique for successful culturing and transplanting of DPC could be perfected. Lastly, the need for more invasive
surgical procedures such as Alopecia Reduction, Scalp Expansion and Extension, and scalp flaps could be eliminated.
In the summer of 1997, Professor Dan Sauder, chief of the Department of Dermatology at the University of Toronto,
Gulnar M. Shivji, Shabana Shahid, and Dr. Walter Unger, met and decided on a series of steps for the investigation of
cloning in humans. Their work is summarized as follows:
Identify and Grow Hair Dermal Papilla Cells (DPC) in culture.
Perfect techniques to grow large numbers of DPC quickly i.e. ideal culture media and nutrients.
Introduce the DPC into athymic mice or SCID mice and grow hair.
Introduce DPC into the human donor skin and grow hair.
Devise optimal methods of introduction of DPC into the human donor.
Learn how to grow hair with uniform density, with growth in the correct direction and at the correct angle.
Although it was initially thought that accomplishing the first two steps would be relatively easy, nearly a year was spent
completing that task. Table #1 outlines the process of identification and characterization of human DPC. The first step in
obtaining DPC involves dissecting the dermal papilla from a small graft containing one or more hairs in the anagen phase
of growth. The dermal papilla is carefully excised from the remaining hair structure and placed into a tissue culture dish
containing medium. These cells may or may not be DPC, and one must learn how to distinguish between them and
epithelial cells or endothelial cells, which inhabit the same area of the follicle. Once the cells grow in culture, their true
identity as DPC are confirmed with three different types of tests. The first is a morphological comparison, the second is
confirmation using antibody stains that specifically react with components of only DPC, and the third is electron
microscopy in which the ultrastructure is studied and confirmed to be that of DPC rather than epithelial or endothelial
cells.
It should be clear from the above, that the task is not as simple as many of us clinicians would believe. Cells can be
incorrectly thought to be DPC, primary cultures are easily contaminated by bacteria, the cells of some patients seem to
22 of 28
The Future in Hair Transplantation - NHI
23 of 28
grow far more easily than others, and finally propagating cells by sub-culturing is sometimes successful and sometimes
not. In addition, the morphologic characteristics of DPC tend to change as their passage numbers are increased and they
also will probably ultimately prove to be less effective in producing hair when they are finally introduced into the test
animals.
Despite the above, we are very positive that we can now get millions of functioning DPC cells from one cell in most
patients and that we will probably be able to do this successfully in all patients with further development of our expertise.
Studies on athymic mice will begin as soon as approval has been received from the ethics committee of the University of
Toronto.
After further refining laboratory studies, we will eventually be ready to introduce the cells into the human donor from which
they came. Should we be successful in growing hair, the remaining two stages - that of devising the optimal methods of
introducing the DPC into the donor and learning how to grow these hairs with a uniform density, in the correct direction
and at the correct angle remain as large clinical barriers we have to overcome.
REFERENCES
J. Embriol: Exp. Morph. August 1967; 8(1): 43-51.
Oliver R.F.: Ectopic Regeneration of Whiskers in the Hooded Rat from Implanted Lengths of Vibrissa Follicle Wall.
J. Embriol. Exp. Morph. 1967; 17: 27-34.
Embryonic Papillae, Edward J. Kollar: The Induction of Hair Follicles. The Journal of Investigative Dermatology
1970; 55(6): 374-378.
Genetic Therapies for Androgenetic Alopecia
Imagine that in your practice in the year 2010, in the corner of the room stands a futuristic incubator full of tiny plastic
dishes with living, growing human dermal papilla cells from anonymous donors with a whole spectrum of different hair
colors and textures. Each of the dermal papilla micro-cultures was already genetically engineered with an ensemble of
genes known to control the growth, cycling and color of the hair for a lifetime. In addition, the grafts were engineered to be
universal donors, by de-programming their immune imprint and re-setting the imprint to that of the recipient. Your patient
enters the room, prepared for today's "treatment", which involves filling your gene gun with papilla micro-cultures, and
permanently implanting engineered cells into the scalp. These magical cells have the ability to perfectly recapitulate the
individual's entire genetic hair program, for the rest of the recipient's life. Should your patient need a little fine-tuning, no
problem - a topically applied growth factor cream to selectively activate and silence the artificial ensemble of genes will do
the trick.
Sounds like science fiction? Think again. For the first time ever, Dermatologic scientists have begun to take aim at a
genetic understanding of androgenetic alopecia (AGA), and if the current pace keeps up, we will have a good handle on
the genes governing the human hair cycle in the next few years. The first human gene known to be involved in control of
hair cycle regulation is called "hairless". It was cloned in our laboratories earlier this year, and proven to be the genetic
cause of a simple form of inherited atrichia1. We anticipate it will be the first of many genes which work together to drive
the hair cycle. With discoveries like this, we will soon be in a position to design rational cell-based and gene-based
therapies for hair loss, in contrast to the currently available treatments. If all of this sounds just around the corner,
however, we must pause and realize that the identification of susceptibility genes for AGA is still a few years away, not to
mention the translation of those genes into a meaningful and rational cellular or genetic therapy.
If we look back in history, it is clear that we are poised for a genetic revolution in our understanding of hair growth at its
most fundamental level. Here, we outline our current thinking of AGA as a complex genetic trait, and discuss our
strategies to identify susceptibility genes for AGA. It is never too early to imagine what the practice of dermatology will be
like in the year 2010, and we believe the future holds great promise for the application of this knowledge in the clinical
setting.
THE HISTORICAL PERSPECTIVE
Correspondence shows that John D. Rockefeller Sr.'s problem with hair loss began in 1886 at the age of forty-seven,
when he began ordering bottles of hair restorative. In 1893, his alopecia worsened as he struggled with digestive
problems and fretted over the University of Chicago's finances. Alopecia totalis, or the total loss of body hair, has been
attributed to many causes, ranging from genetic factors to severe stress, but remarkably little is known for certain. In
March of 1901, his symptoms worsened markedly, his moustache began to fall out, and all the hair on his body had
followed by August.
The change in his appearance was startling. He suddenly looked old, puffy, stooped, and all but unrecognizable. He
seemed to age a generation. Without hair, his facial imperfections grew more pronounced. His skin appeared parchment
dry, his lips too thin, his head large and bumpy. Soon after losing his hair, Rockefeller went to a dinner thrown by J.P.
Morgan (one of the few public dinners he ever attended) and sat down next to a mystified Charles Schwab, the new
president of U.S. Steel. "I see you don't know me, Charley," said Rockefeller.
"I am Mr. Rockefeller".
The Future in Hair Transplantation - NHI
24 of 28
Coming on the eve of the muckraking era, Rockefeller's alopecia had a devastating effect on his image: It made him look
like a hairless ogre, stripped of all youth, warmth and attractiveness, and this played powerfully on people's imaginations.
For a time, he wore a black skullcap, giving him the impressively gaunt physiognomy of a Renaissance prelate. One
French writer wrote "under his silk skull-cap he seems like an old monk of the inquisition such as one sees in the Spanish
picture galleries."
The alopecia dealt a blow to Rockefeller's morale. The psychological effect is crushing for most people, and he dabbled
restlessly in remedies. His physician started him on a hair-restoration regimen in which he took phosphorus six days a
week and sulfur on the seventh. When such remedies failed, Rockefeller decided to buy a wig. Self-conscious at first and
reluctant to wear it, he tested it one Sunday at the Euclid Avenue Baptist Church. Before the service, he stood in the
pastor's office, nervously adjusting it and telling a listener what an ordeal it would be to wear it in the church. When the
wig met with a good reception, he was almost boyishly elated. Soon, he grew to love this wig, telling daughter Edith, "I
sleep in it and play golf, and I am surprised that I went so long without it, and think I made a great mistake in doing so."
He became so fond of wigs that he started to wear rotating wigs of different lengths to give the impression of his hair
growing and then being cut. He even had wigs styled for different occasions: golf, church, short walks, and so on. For all
his wealth, however, Rockefeller could never find the ideal wig. Starting out with a fashionable wig maker on the Rue
Castiglione in Paris, he grew disillusioned when springs in the framework pushed up through the hair. He then switched to
a Cleveland wig maker whose product had another maddening defect: The foundation fabric would shrink, making the wig
suddenly slide across his bald pate.
What God had taken away, it seems, could never be perfectly restored.
- excerpted from Titan by Ron Chernow, 19982
This passage from a recent biography of John D. Rockefeller, Sr. captures the essence of living with alopecia from the
standpoint of the patient2. We empathize with his fruitless searching for remedies, we are humbled and moved by the
erosion of his self-esteem, we are chilled by the description of his ghoulish appearance, we cheer when his wig is met
with approval in the church, we laugh and cry with him at the tales of him searching the globe for the perfect hairpiece,
and we are intrigued by the observation revealed later in the book that his mother suffered from the same condition.
Equally chilling, however, is the observation that in the 100 years since Rockefeller's alopecia began, at least three things
remain unchanged: the devastation of its victims, the absence of a cure, and importantly, the profound lack of scientific
knowledge about its pathogenesis.
A century later, with the advent of modern genomics, we stand uniquely poised to bring an end to all three.
THE ANSWERS ARE IN OUR GENES
Alopecia areata (AA) affects approximately 1.7% of the United States population, or approximately 4.6 million individuals,
including males and females of all ages and ethnic groups3,4. A second, more common form of hair loss, androgenetic
alopecia (AGA), also known as male pattern baldness, affects 50% of all males over age 50 in the United States, and a
large percentage of women, generating a combined figure of nearly 40 million individuals who suffer from some form of
inherited hair loss5-7, most of whom spend billions of dollars each year on ill-designed treatments, not cures, to combat
their disease. While it is clear that AGA is a hormonally-modulated phenotype, it is clearly not due to single gene
mutations in a single gene, such as the 5ða-reductase genes8,9, and it fits the criteria to be modeled and analyzed as a
primary polygenic disorder for the first time.
In men with AGA, the reported effects of hair loss are: considerable preoccupation, stress, anxiety, and coping
efforts10,11. These effects are more pronounced in men with extensive hair loss, and among younger, single men, and
those with an early onset of hair loss. Relative to control subjects, balding men had less body-image satisfaction yet were
comparable in other personality indexes. Although most men regard hair loss to be an unwanted and distressing
experience that damages their body image, many balding men actively cope and generally retain the integrity of their
personality functioning10,11.
In contrast, similar research revealed strikingly deleterious psychosocial effects of AGA in women12,13. The vast majority
reported that their hair loss engendered considerable anxious preoccupation, helplessness and feelings of diminished
attractiveness. Women worried that others would notice their hair loss and that the condition would progress and become
more socially apparent. Such stresses also gave rise to active coping efforts. Many have sought information and selective
social support, struggled to control their disruptive negative thoughts and feelings about their condition, tried to conceal
their hair loss with altered hairstyles, and engaged in compensatory grooming activities to try to restore their body-image
integrity. AGA was clearly more disturbing to affected women than a control group of women with less visible cutaneous
disorders, and the psychological impact of androgenetic alopecia was found to be two-fold higher in women than in
men12,13.
The authors of these studies emphasize that physicians should recognize that the pathology of AGA goes well beyond
the physical aspects of hair loss and growth10-13. As has been observed in other appearance-altering conditions, they
noted that patients' psychological reactions to hair loss were less related to the clinician's ratings than to the patient's own
perceptions of the extent of their hair loss. Even in patients with minimal hair loss, that loss carries significant emotional
The Future in Hair Transplantation - NHI
25 of 28
and psychological meaning that the physician should not minimize. The losses pertain not only to hair, but profoundly
impact the quality of life, the ability to function in society, the preservation of self-esteem, and can lead to psychological
disturbances as profound as suicide. One recent statistic quoted that 45% of men with AGA would sacrifice 5 years of
their life span for a full head of hair14.
The two prescription drugs currently available for AGA are largely unsatisfactory, and were serendipitously found to grow
hair in men taking these drugs for other indications, including hypertension and prostate hypertrophy. Astonishingly,
neither of these treatments arose from primary research on the genetic mechanisms driving the hair cycle. Similarly, a
rationally designed treatment for AA based on a fundamental understanding of the disease process is sorely lacking.
Desperate patients spend tens of millions of dollars a year for remedies, yet all of this is in vain in the absence of a basic
knowledge of hair loss as a genetically controlled process. Only genetic therapies targeting the hair cycle itself will lead to
a cure for hair loss, in contrast to the available treatments which ineptly address only downstream effects.
For the first time in history, we are in a position to address these devastating dermatologic diseases from their foundation,
as complex genetic disorders. With the promise of completion of the Human Genome Project in 2005, these studies are
timely in a way not possible up to now, and will likely lead to the identification of candidate susceptibility genes by the end
of the five years15.
We present a strategy for the identification of candidate genes in the control of the hair cycle, starting with simple
Mendelian forms of inherited alopecia, and expanding into genome-wide linkage studies in complex genetic diseases
including AGA. These studies will pinpoint candidate genes for the first time, lead to an understanding of the interactions
of these genes with each other and with other variables such as the immune system and hormonal differences, and
ultimately illuminate potential rational therapeutic targets for the future.
MALE PATTERN BALDNESS AS A COMPLEX TRAIT DISORDER
Mendelian forms of diseases such as inherited alopecias are rare, clear cut, black-and-white examples of disease
segregation: a family member can either be affected or unaffected. Mendelian traits 'run in families' (segregate) in clear
and reproducible patterns, usually autosomal recessive or dominant.
The term "complex trait", in contrast, refers to a more common genetic disorder that appears as a spectrum of shades of
gray, rather than black and white. This term is used to describe any phenotype that does not exhibit classic Mendelian
recessive or dominant inheritance attributable to a single gene locus15-18. The genes contributing to the phenotype can
exist in such a way that they confer either additive or multiplicative degrees of susceptibility to developing disease15. The
genetic analysis of complex non-Mendelian traits is most efficiently and powerfully studied using a technique known as
Affected Sib Pair (ASP) analysis19-25. For two parents considered jointly, the two offspring can either share 0, 1, or 2
alleles with an average of 1 under no linkage. Testing for linkage amounts to determining whether the observed number of
alleles shared over many ASPs is significantly higher than expected by chance, a phenomenon known as IBD, or identity
by descent.
Once a complex trait has been mapped to several susceptibility loci, the formidable task of identifying the responsible
gene still remains. Up to now, this has proven the greatest challenge in complex trait analysis, however, the timeliness of
this proposal is reflected in the promise of the Human Genome Project to make a tremendous contribution to the
positional cloning of complex traits by eventually providing a complete database of all genes in a given region15. Upon its
completion near the year 2004, the Human Genome Project will facilitate the rapid and systematic evaluation of candidate
genes in inherited alopecias.
The starting point for the genetic dissection of complex traits lies in the demonstration that genes are indeed an important
part of whether an individual is at increased risk for disease predisposition. The observation that a trait 'runs in families'
(aggregates) in an ill-defined pattern is not sufficient evidence to make the a priori assumption that its etiology is genetic,
since families may share predisposing environments as well as genes. With this starting point in mind, we present the
following arguments in favor of polygenic inheritance model in AGA.
IS ANDROGENETIC ALOPECIA GENETIC?
It has been widely cited in the Dermatologic literature that AGA is caused by a single autosomal dominant gene with
reduced penetrance in women3,6,12,26. Amazingly, there exists only a single extensive family study published by
Dorothy Osborn in 1916, where she studied the pattern of hair growth in 22 families and concluded that AGA is an
autosomal dominant phenotype in men and a recessive phenotype in women27. She believed that a single gene dosage
(Bb) causes AGA in men, where a double dose (BB) would be necessary in women. She gave no details regarding the
methods of her examination, and weakened the validity of her data by stating that she had simply omitted the
symptom-free women in her pedigrees27,28. Nonetheless, her conclusions were adopted, cited, and re-cited until the
present, by many writers in both the dermatologic and genetic literature.
While careful family studies of AGA are still lacking, in 1984, Küster and Happle reconsidered the autosomal dominant
model of AGA, and put forth several arguments against a simple mode of Mendelian inheritance. What they did, in fact,
was to meticulously define AGA as a classic example of a polygenic trait28.
The Future in Hair Transplantation - NHI
26 of 28
First Argument: Prevalance of the AGA Trait
It is common knowledge that AGA is widespread in all populations, yet it is difficult to determine the exact frequency of the
trait. Numbers in the literature vary, however, a generally accepted rule of thumb is that approximately 50% of 50-year old
men will have AGA, thus, affecting approximately 30 million men in the U.S.3,12,26.
Hereditary traits due to a single gene rarely occur with a frequency higher than 1:1000. If AGA were a dominant trait
resulting from a single gene, then it would be predicted that only 270,000 individuals in the U.S. would be affected. As a
general rule, inherited traits with a higher prevalence are due to more than one gene, therefore, the prevalence of AGA is
a strong argument in favor of polygenic transmission28.
Second Argument: The Normal Gaussian Curve of Distribution
There is no generally accepted borderline between "normal" men and individuals with AGA. Any attempt to draw the line
would be arbitrary, and in fact, all stages ranging from full hair growth to complete baldness are found in the population,
with the transitions between these stages being fluid. The prevalence of AGA corresponds to a normal gaussian (bell)
curve of distribution, typical of polygenic traits. If AGA were due to a single gene, there would be a clear-cut difference
between the phenotypes, and we would expect a curve with two or more peaks28.
The distribution of AGA is best explained by a model of polygenic inheritance with a threshold effect. Individuals on the far
left of such a curve represent those who carry only a few predisposing genes, and therefore enjoy a lifelong full head of
hair. For those in the middle curve, there is a threshold for the manifestation of the trait, and the threshold is lowered by
the presence of circulating androgens28. The essential role of androgens in the development of AGA is reflected in the
nomenclature "andro" "genetic", since it is believed that androgens alone cannot produce AGA without an inherited
predisposition, and the inherited predisposition cannot produce AGA in the absence of androgens5,28.
Third Argument: Risk Increases with the Number of Family Members Already Affected
In 1946, Harris examined 900 men and found a "premature baldness" in 120 of them29. In this group, he determined the
number of affected brothers in families with an affected father, as well as in families with an unaffected father. He showed
that the number of affected brothers was higher in families that also had an affected father. If AGA were due to a single
autosomal dominant gene, there should be no difference between the two groups. In contrast, a model of polygenic
transmission would suggest that there should be a difference, since the risk of an individual developing AGA would
increase with the number of family members already affected28.
Fourth Argument: Severely Affected Women Carry More Predisposing Genes that Mildly Affected Women
In 1964, Smith and Wells studied the first-degree relatives of 56 women with AGA30. Eighteen of these women had
severe AGA, and interestingly, these 18 women had more affected first-degree relatives as compared to the entire group
of 56 women. Smith and Wells postulated that the severely affected women were homozygous for a dominant gene, but
they emphasized that this would not explain the fact that only 33% and not 100% of the fathers of these women were
affected. This observation argues against the assumption of simple Mendelian inheritance, and also cannot be explained
by the auxiliary hypotheses of diminished penetrance and variable expressivity. However, the model of polygenic
inheritance provides an explanation for the results obtained by Smith and Wells: In the severely affected women, the
number of predisposing genes is higher than in the mildly affected women, and therefore, more first-degree relatives will
be affected28.
Fifth Argument: Affected Women Carry More Predisposing Genes Than Affected Men
In 1890, Jackson examined 1,200 individuals with "premature baldness", consisting of 410 men and 790 women31. In the
group of 410 men, he found a genetic influence from the father's side in 236 cases, from both parents in 27 cases, and
from the mother's side in 9 cases. In the group of 790 women, he found 131 affected fathers and 240 affected mothers.
This would be consistent with the assumption that for affected women, the maternal predisposition is more important than
the paternal predisposition. However, the threshold concept provides an explanation that is more plausible than assuming
homozygosity in severely affected women. Due to the higher androgen threshold present in women, an affected woman
would carry a higher number of predisposing genes than a man affected to the same degree, and therefore, she would
transmit a higher number of predisposing genes to her offspring28.
SUMMARY
The discovery of genes directly implicated in the pathogenesis of inherited hair loss will have far-reaching implications for
the treatment of affected individuals. Ultimately, it is hoped that discovery and modulation of the genes for inherited hair
loss will provide novel therapeutic targets, and eventually eliminate these psychologically devastating disorders.
REFERENCES
Ahmad, W., Ul Haque, M. F., Brancolini, V., Tsou, H. C., Ul Haque, S., Lam, H., Aita, V. M., Owen, J., deBlaquiere,
M., Frank, J., Cserhalmi-Friedman, P. B., Leask, A., McGrath, J. A., Peacocke, M., Ahmad, M., Ott J., Christiano,
A. M.: Alopecia Universalis Associated with a Mutation in the Human Hairless Gene. Science 1998; 279: 720-724.
The Future in Hair Transplantation - NHI
Chernow, R.: Titan: The Life of John D. Rockefeller, Sr. Random House, New York 1998; 192: 407-408.
Sawaya, M.E., Hordinsky, M.K.: Advances in Alopecia Areata and Androgenetic Alopecia. Adv. Dermatol 1992;
211-226.
Schwartz, R.A., Janniger, C.K.: Alopecia Areata. Cutis 1997; 59: 238-241.
Kaufman, K.D.: Androgen Metabolism as it Affects Hair Growth in Androgenetic Alopecia. Dermatol. Clin. 1996; 14:
697-711.
Roberts, J.L.: Androgenetic Alopecia in Men and Women: An Overview of Cause and Treatment. Dermatol. Nurs.
1997; 9:379-386.
Drake, L.A., Dinehart, S.M., Farmer, E. R., Goltz, R.W., Graham, GAF., Hordinsky, M.K., Lewis, C.W., Pariser,
D.M., Webster, S.B., Whitaker, D.C., Butler, B., Lowery, B.J., Price, V.H., Baden, H., DeVillex, R.L., Olsen, R.,
Shupack, J.L.: Guidelines of Care for Androgenetic Alopecia. American Academy of Dermatology. J. Am. Acad.
Dermatol. 1996; 35: 465-469.
Sawaya, M.E., Price, V.H.: Different Levels of 5 Alpha-Reductase Type I and II, Aromatase and Androgen
Receptor in Hair Follicles of Women and Men with Androgenetic Alopecia. J. Invest. Dermatol. 1997; 109: 296-300.
Ellis, J.A., Stebbing, M., Harrap, S.B.: Genetic Analysis of Male Pattern Baldness and the 5ða-Reductase Genes.
J. Invest. Dermatol. 1998; 110: 849-853.
Cash, T.F.: The Psychological Effects of Androgenetic Alopecia in Men. J. Am. Acad. Dermatol. 1992; 26: 926-931.
Maffei, C., Fossati, A., Rinaldi, F., Riva, E.: Personality Disorders and Psychopathologic Symptoms in Patients with
Androgenetic Alopecia. Arch. Dermatol. 1994; 130: 868-872.
Spindler, J.R., Data, J.L.: Female Androgenetic Alopecia: a Review. Dermatol. Nurs. 4: 93-99, 1002.
Cash, T.F., Price, V.H., Savin, R.C.: Psychological Effects of Androgenetic Alopecia on Women: Comparisions with
Balding Men and With Female Control Subjects. J. Am. Acad. Dermatol. 1993; 29: 568-575.
American Hair Loss Council, Chicago, IL.
Lander, E.S., Schork, N.J.: Genetic Dissection of Complex Traits. Science 1994; 265: 2037-2048.
Kruglyak, L., Lander, E.S.: High-Resolution Genetic Mapping of Complex Traits. Am. J. Hum. Genet. 1995;
56:1212-1223.
Ott, J.: Complex Traits on the Map. Nature 1996; 379: 772-773.
Kruglyak, L., Lander, E.S.: Complete Multipoint Sib-Pair Analysis of Qualitative and Quantitative Traits. Am. J.
Hum. Genet. 1995; 57: 439-454.
Weeks, D.E., Lathrop, G.M.: Polygenic Disease: Methods for Mapping Complex Diseases Traits. Trends Genet.
1995; 11: 513-519.
Knapp, M., Seuchter, S.A.,Baur, M.P.: Linkage Analysis in Nuclear Families. 2: Relationship Between Affected
Sib-Pair Tests and Lod Score Analysis. Hum. Hered. 1994 4: 44-51.
Knapp, M., Seuchter, S.A., Baur, M.P.: Linkage Analysis in Nuclear Families. 1: Optimality Criteria for Affected
Sib-Pair Tests. Hum. Hered. 1994; 44: 37-43.
Holmans, P., Craddock, N.: Efficient Strategies for Genome Scanning Using Maximum-Likelihood Affected-sib-pair
Analysis. Am. J. Hum. Genet. 1997; 60: 657-666.
Kruglyak, L. Lander, E.S.: A Nonparametric Approach for Mapping Quantitative
Trait Loci. Genetics 1995; 139:1421-1428.
Fulker, D.W., Cherny, S.S.: An Improved Multipoint Sib-pair Analysis of Quantitative Traits. Behav. Genet. 1996;
25:527-532.
Risch, N.: Linkage Strategies for Genetically Complex Traits. II. The Power of Affected Relative Pairs. Am. J. Hum.
Genet. 1990; 46:229-241.
Bergfeld, W.F.: Androgenetic Alopecia: An Autosomal Dominant Disorder. Am. J. Med. 1995; 98: 95S-98S.
Osborn, D.: Inheritance of Baldness. J. Hered.1916; 7: 347-355.
Küster, W, Happle, R.: The Inheritance of Common Baldness: Two B or not Two B? J. Am. Acad. Dermatol. 1984;
11:921-926.
Harris, H.: The Inheritance of Premature Baldness in Men. Ann. Eugenics 1946; 13: 172-181.
Smith, M.A. and Wells, R.S.: Male-Type Alopecia, Alopecia Areata, and Normal Hair in Women. Arch. Dermatol.
1964; 89: 155-158.
Jackson: Diseases of the Hair and Scalp. New York, 1890. (cited according to Galewsky, E. Erkrankungen der
Haare und des Haarbodens, in Jadassohn J, editor: Handbuch der Haut und Geschlechtskrankheiten. 1932
Springer-Verlag, Vol. 13, pp.216-220.)
A History Lesson 1
In 1983, at a hair replacement symposium in Los Angeles, a single case report of transplanting only ten two-haired
micrografts to refine an abrupt standard grafted hairline was presented. The speaker was careful to mention that
harvesting and planting 10-15 micrografts in each standard grafting session, and placing them on the part-side only,
would add only ten or fifteen minutes of additional time to the length of each surgical session.
No sooner had the presentation ended when a distinguished dermatologic surgeon rose from his seat and announced to
the other three hundred members of the audience, "This lecture was the greatest waste of time I have ever been forced to
sit and listen to. The hair transplant procedure is tedious and time-consuming enough without adding another fifteen
minutes for only fifteen more hairs. Besides my patients are already very happy with their results. I hardly think a few
more isolated single hairs would make any difference to them." No one in the room rose to refute him.
27 of 28
The Future in Hair Transplantation - NHI
28 of 28
One year later that presentation was published in the Journal for Dermatologic Surgery!2 Dr. Art Ulene, then the medical
correspondent for the Today Show, read it, contacted the speaker, filmed the process, and broadcasted it to a national
television audience. The rest, as they say, is history. Apparently those legions of supposedly "happy patients" concluded
quite independently from their doctors, that those "few isolated single hairs" just might make them even happier that they
already were! Unlike their surgeons, they saw a great deal of difference, indeed. Protestations of additional time and
tedium meant nothing to them…that was the doctor's problem. They cared only how they looked.
The future of hair replacement surgery will be determined, not by the doctor, but by the patient. The fully informed patient,
the educated, savvy hair consumer is the most feared and powerful species in the free enterprise jungle of surgical hair
replacement. His power comes from his knowledge. Comfortable and complacent surgeons should be wary. Though Dr.
Art Ulene has retired, it will only be a matter of time before some other enterprising investigative, reporter decides once
again to educate the "happy" hair consumer. Then, as in 1983, the rest will be history, and those who cannot remember it
will be condemned to repeat it.
REFERENCES
Marritt, E: Full text to be published in Hair Transplant Forum International.
Marritt, E: Single-hair Transplantation for Hairline Refinement: A Practical Solution. Journal for Dermatologic
Surgery and Oncology Dec'84; 10(12): 962-66.
Acknowledgment: The authors would like to thank Rebecca Sipala, Nazia Rashid and Marie Rassman for their assistance
in the preparation of this manuscript.
Reprint Requests:
Robert M. Bernstein, MD
125 East 63rd Street, New York, New York 10021
Tel: 212-826-2400 Fax: 201-585-0464
• Back to Medical Publications
© 2013 New Hair Institute.
www.newhair.com